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[(merous)-262.8(studies)-257.5(have)-256.5(documented)-257.2(increased)-263.4(levels)-255.5(of)-256.2(reactive)]TJ 0 -1.2203 TD [(products)-275.8(of)-268.8(lipid)-274.2(peroxidation)-269.7(in)-272.5(diseased)-270.7(regions)-275.3(of)-268.8(brain)-270.8(in)]TJ T* [(different)-460.8(brain)-454.2(disorders)-458.8(\(32,)-451.3(72,)-457.2(194\).)-450.8(Consistent)-459.3(with)-457.9(the)]TJ 0 -1.2266 TD [(importance)-419.5(of)-414.2(lipid)-419.6(peroxidation)-415.1(in)-417.9(neurodegenerative)-421.8(dis-)]TJ 28.0042 74.5534 TD [(eases,)-257.8(proteins)-260(modied)-253(by)-255.4(lipid)-255.2(peroxidation)-263.4(products)-256.9(were)]TJ 0 -1.2203 TD [(present)-411.7(in)-411.6(diseased)-416.1(regions)-414.4(of)-414.2(the)-408.4(brain)-416.2(but)-410.9(not)-411.3(in)-411.6(regions)]TJ 0 -1.2266 TD [(uninvolved)-281.6(in)-285.1(the)-282(disease)-280.4(\(32\).)]TJ /F3 1 Tf 0 -2.4406 TD [(Lipid)-333.8(Peroxidation:)-336.6(vlogٷ)-338.1(and)-331.9(Products)]TJ /F5 1 Tf 1.1128 -1.8336 TD .0102 Tc 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6.7246 0 0 5.9768 377.1779 625.6628 Tm ($)Tj /F5 1 Tf 8.9663 0 0 8.9663 380.1826 621.6943 Tm [(,)-319.1(p)0(e)17.7(r)0(o)21.8(x)0(y)18.7(l)-319.7(RO)18(O)]TJ /F10 1 Tf 6.7246 0 0 5.9768 437.2156 625.6628 Tm ($)Tj /F5 1 Tf 8.9663 0 0 8.9663 440.2203 621.6943 Tm [(,)-319.1(a)0(n)16.1(d)-319.1(po)14.8(ss)22.7(ib)17.3(ly)-311.4(H)12.7(O)]TJ 6.7246 0 0 5.9768 512.1069 620.1636 Tm (2)Tj /F10 1 Tf .489 .9201 TD ($)Tj /F5 1 Tf 8.9663 0 0 8.9663 521.3479 621.6943 Tm [(bu)19.5(t)-322.9(n)0(o)19.1(t)]TJ -23.477 -1.2266 TD (H)Tj 6.7246 0 0 5.9768 318.2739 609.2219 Tm (2)Tj 8.9663 0 0 8.9663 321.7322 610.6959 Tm (O)Tj 6.7246 0 0 5.9768 328.8755 609.2219 Tm (2)Tj 8.9663 0 0 8.9663 336.4156 610.6959 Tm .0091 Tc [(or)-459.5(O)]TJ 6.7246 0 0 5.9768 356.0881 609.2219 Tm 0 Tc (2)Tj /F9 1 Tf .6829 .9201 TD (-)Tj /F10 1 Tf .7335 0 TD ($)Tj /F5 1 Tf 8.9663 0 0 8.9663 368.6172 610.6959 Tm [(\))-468.4(a)-12.2(tt)-19.9(ac)-17.8(k)-10.7(s)-469.2(a)-467.4(m)-10.2(et)-19.3(h)-9.7(y)-10.7(l)-9.9(e)-12.5(n)-9.7(e)-467.8(g)-10.7(r)-7(o)-15.4(u)-7.7(p)-469.2(i)-9.9(n)-465(t)-13.1(h)-9.7(e)-467.8(P)-7.7(U)-14(F)-10.7(A)-7.7(s)-14(,)]TJ -6.443 -1.2203 TD .0109 Tc [(lea)10.9(d)-4.3(in)-5.1(g)-246.4(t)10.9(o)-257.9(a)-1.3(n)-245.4(a)-1.3(llylic)-247.6(H)-248.3(a)-1.3(tom)-245.9(a)-1.3(bstra)10.9(c)-6.9(tion)-245.4(with)-245.4(re)10.9(a)-7.5(r)-2.5(range)10.9(m)-5.5(ent)]TJ T* .3855 Tc [(o)376.4(f)-.7(t)385.5(h)369(ed)376.2(o)370.1(u)377.8(b)374.8(l)375.6(eb)374.8(o)376.4(n)375.8(d)376.2(s)-1.5(t)385.5(o)-3.4(t)372.4(h)375.8(ec)373.6(o)376.4(n)375.8(j)374.2(u)377.8(g)374.8(a)373.3(t)372.4(e)385.5(dd)369.9(i)375.6(e)385.5(n)363.2(e)6.2(f)372.4(o)376.4(r)372.2(m)375.3(,a)385.5(n)363.6(d)3.1(s)377.9(i)375.6(-)]TJ 0 -1.2266 TD .011 Tc [(multane)11(o)-10.6(usly)-284.3(pro)-4.4(d)1.7(ucing)-290.6(a)-292(ca)11(r)-8.2(b).3(on-c)11(e)-7.2(n)1.3(tered)-289.2(a)-1.2(lky)11(l)-294.1(radica)11(l)-4.7(.)-289.1(In)]TJ 0 -1.2203 TD 0 Tc [(s)-7.6(t)-13.1(e)-12.5(p)-279.6(2)-12.2(,)-287.4(th)-16.5(e)-284.4(a)-12.2(l)-9.8(k)-10.7(y)-10.7(l)-281.7(r)-13.3(a)0(d)-21.5(i)-9.9(ca)-17.8(l)-281.7(r)-13.3(e)-12.5(a)0(c)-17.8(t)-13.1(s)-285.8(w)-7.9(i)-9.9(t)-13.1(h)-281.6(p)-14(ar)-19.2(am)-16(a)-12.2(g)-10.7(n)-9.7(e)-12.6(ti)-16.6(c)-290.1(m)0(o)-19.3(l)-9.9(ec)-18.2(u)-14(l)-9.8(ar)]TJ T* [(o)-9.1(x)-8.5(y)-10.7(g)-10.7(e)-12.5(n)-237.3(t)-13.1(o)-236.7(f)-13.1(o)-9.1(r)-7(m)-244.2(a)-233.5(p)-14(e)-12.5(r)-7(o)-9.1(x)-14.8(y)0(l)-248.2(r)-7(a)-12.2(d)-9.3(i)-9.9(c)-11.9(al)-15.7(.)-243.2(P)-7.7(r)-13.3(o)-9.1(p)-7.7(a)-12.2(g)-10.7(a)-12.2(ti)-16.7(o)-15.4(n)-237.3(o)-9.1(c)-11.9(c)-11.9(u)-7.7(r)-13.3(s)-235.3(i)-9.9(n)-243.7(s)-7.6(t)-13.1(ep)]TJ 0 -1.2266 TD .0108 Tc 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[(o)-9.1(x)-8.5(i)-9.9(d)-9.3(e)-12.5(s)-380.7(c)-11.9(a)-12.2(n)-376.4(b)-10.7(e)-379.3(f)-13.1(u)-7.7(r)-13.3(th)-22.8(er)-386.3(d)-9.3(e)-12.5(g)-10.7(r)-13.4(ad)-15.2(e)-12.5(d)-382.4(to)-388.9(h)-9.7(y)-10.7(d)-9.3(r)-13.3(o)-9.1(c)-11.9(ar)-19.2(b)-10.7(o)-9.1(n)-9.7(s)-14(,)-376(a)-12.2(l)-9.9(c)-11.9(o)-9.1(h)-9.7(o)-9.1(l)-9.8(s)-14(,)]TJ T* [(et)-19.3(h)-9.7(e)-12.5(r)-13.3(,)-432.9(ep)-20.2(o)-9.1(x)-8.5(i)-16.2(d)-9.3(es)-20.2(,)-432.9(a)-12.2(n)-9.7(d)-433(a)-12.2(l)-9.9(d)-9.3(e)-12.5(h)-9.7(y)-10.7(d)-9.3(e)-12.5(s)-7.6(.)-432.9(O)-9.4(f)-436.8(t)-13.1(h)-9.7(e)-12.5(s)-7.6(e)-436.2(p)-14(r)-7(o)-9.1(d)-9.3(u)-14(c)-11.9(t)0(s)-20.8(,)-432.9(M)-11.4(D)-7.7(A)-14(,)]TJ T* .0102 Tc [(H)10.2(N)-8.7(E,)-466.9(and)-467(a)10.2(c)-7.6(r)-3.1(olein)-467.4(c)10.2(a)-7.6(n)-467.4(ca)10.2(u)-9.6(s)2.6(e)-470.2(i).3(rreversible)-463.9(m)0(od)-5.4(ic)10.2(a)-7.6(tion)-467.4(of)]TJ 0 -1.2266 TD .0119 Tc [(p)4.2(h)2.2(os)4.3(pholipids)4.3(,)-509.5(pr)4.9(oteins)4.3(,)-509.5(a)-.3(nd)-509.6(DN)11.9(A)-520.6(r)4.9(es)4.3(ult)11.9(i)-4.7(ng)-504.7(in)-510(impa)11.9(i)-10.1(r)4.9(ed)]TJ 0 -1.2203 TD 0 Tc [(fu)-20.8(n)-9.7(c)-11.9(ti)-23(o)-9.1(n)-332.2(\()-13.1(6)-12.2(9\))-19(.)-331.7(I)-14.8(n)-332.2(s)-14(te)-19.3(p)-336.5(4)0(,)-343.9(t)0(e)-19.3(r)-13.3(m)-10.2(i)-9.9(n)-9.7(a)0(t)-19(i)-9.9(o)-9.1(n)-338.5(o)-9.1(c)-11.9(c)-11.9(u)-7.7(r)-13.3(s)-7.6(,)-338(i)-9.9(n)-332.2(w)-14.3(h)-9.7(i)-9.9(c)-11.9(h)-332.2(d)-9.3(i)-9.9(r)-13.3(e)0(c)-18.1(t)]TJ T* .0107 Tc [(inte)10.7(r)-8.9(a)-1.5(c)10.7(t)-8(ion)-530.1(b)0(et)10.7(w)-10.4(e)10.7(e)-8.1(n)-530.1(diff)10.7(e)-8.6(r)3.7(ent)-533.5(t)10.7(y)-6.8(p)-3.3(e)10.7(s)-534.3(o)-4.7(f)-527.2(radicals)-528.1(block)-524.8(t)-2.4(he)]TJ 0 -1.2266 TD .0109 Tc [(cha)10.9(i)-4.8(n)-213.8(r)-2.5(ea)10.9(c)-6.9(t)-2.2(ion)-213.8(c)-1(a)10.9(s)-8.9(ca)10.9(d)-4.3(e)-1.6(.)-213.3(F).2(inally,)-213.3(i)1(n)-213.8(s)3.3(te)10.9(p)-224.3(5)10.9(,)-219.2(t)-2.2(here)-216.6(is)-211.7(te)10.9(r)-8.7(m).7(inat)10.9(i)-5.7(o)-4.5(n)]TJ 0 -1.2203 TD 0 Tc [(b)-10.7(y)-257.3(i)-9.9(n)-9.7(t)-13.1(e)-12.5(r)-7(a)-12.2(ct)-18.7(i)-9.9(o)-9.1(n)-262.6(b)-10.7(e)-12.5(t)0(w)-21.1(e)0(e)-18.8(n)-262.6(th)-16.5(e)-265.5(r)-7(a)-12.2(d)-9.3(i)-9.9(c)-11.9(al)-15.7(s)-260.5(a)-12.2(n)-9.7(d)-262.2(an)-15.5(t)-13.1(i)-9.9(o)-9.1(x)-14.8(i)-9.9(d)-9.3(an)-21.9(ts)-20.7(,)-255.8(g)-10.7(i)-9.9(v)-13.4(i)-9.9(n)-9.7(g)]TJ T* [(r)-7(i)-9.9(s)-14(e)-290.7(to)-300.4(n)-9.7(o)-9.1(n)-16(r)-7(a)-12.2(d)-9.3(i)-9.9(c)-11.9(al)-300.2(p)-7.7(r)-13.3(o)-9.1(d)-9.3(u)-7.7(c)-11.9(t)-13.1(s)-292.2(o)-9.1(r)-291.6(u)-7.7(n)-9.7(r)-13.3(e)0(a)-18.4(c)-11.9(ti)-23(v)-7.1(e)-290.7(r)-13.3(a)0(d)-15.2(i)-9.8(c)-11.9(a)-12.2(l)-9.9(s)-7.6(.)]TJ 1.1128 -1.2266 TD .0102 Tc 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[(p)-7.7(r)-13.3(o)-9.1(p)-7.7(o)-15.4(s)-7.6(e)-12.5(d)-325.5(t)-13.1(h)-9.7(i)-9.9(s)-323.8(m)-10.2(e)-12.5(c)-11.9(h)-9.7(an)-21.9(i)-9.9(s)-7.6(m)-326.4(b)-10.7(y)-326.9(c)0(o)-21(m)-10.2(p)-7.7(a)-12.1(r)-7(i)-9.9(n)-9.7(g)-326.9(t)-13.1(h)-9.7(e)-328.7(e)0(f)-19.3(f)-13.1(ec)-18.2(t)-13.1(s)-323.8(o)-9.1(f)-329.3(to)-22.2(x)-8.5(i)-9.9(c)]TJ 0 -1.2266 TD [(c)-11.9(o)-9.1(n)-9.7(c)-11.9(en)-22.3(tr)-20.1(at)-19(i)-9.9(o)-9.1(n)-9.7(s)-266.9(o)-9.1(f)-266(H)-12.6(N)0(E)-268.5(o)-15.4(n)-262.6(r)-7(a)-12.2(t)-266(h)-9.7(e)-12.5(p)-7.7(a)-12.2(to)-22.2(cy)-16.3(t)-13.1(e)-12.5(s)-260.5(w)-7.9(i)-16.2(t)0(h)-269.4(a)-12.2(n)-9.7(d)-262.2(w)-14.3(i)-9.9(th)-22.8(o)-9.1(u)-7.7(t)]TJ 0 -1.2203 TD [(p)-7.7(r)-13.3(et)-19.3(r)-13.3(e)0(a)-18.4(t)-13.1(m)-10.2(e)0(n)-15.9(t)-304(w)-7.9(i)-9.9(t)-13.1(h)-300.6(V)-15.5(i)-9.9(ta)-19(m)-10.2(i)-9.9(n)-300.6(E)-9.3(.)-300.1(T)-9.3(h)-16(e)-297.1(p)-14(r)-7(o)-15.4(t)0(e)-19.3(c)-11.9(ti)-16.7(v)-13.4(e)-303.4(ef)-19.3(f)-13.1(e)0(c)-18.2(t)-13.1(s)-298.5(e)-12.5(x)-8.5(e)-12.5(r)-7(t)-13.1(e)-12.5(d)]TJ T* .0109 Tc [(by)-195.9(ant)10.9(i)-5.7(oxidant)-198.2(t)-2.2(owar)3.9(ds)-199.1(HNE)-194.4(and)-200.8(o)1.8(t)10.9(h)-11.9(e)10.9(r)-204.7(toxic)-203.4(a)10.9(ldehydes)-199.1(hav)3.8(e)]TJ 0 -1.2267 TD .0106 Tc [(be)10.6(e)-8.2(n)-245.7(investigat)10.6(e)-8.7(d)-239(by)-240.4(many)-240.4(groups)-243.6(t)10.6(o)-251.9(te)10.6(s)-9.6(t)-242.8(t)10.6(h)-5.9(e)-248.5(p)2.9(ossibility)-240.4(of)-242.8(a)]TJ 0 -1.2203 TD 0 Tc [(th)-22.8(er)-19.6(ap)-19.8(e)-12.5(u)-7.7(t)-13.1(i)-9.9(c)-347(u)-7.7(s)-14(e)-341.3(o)-15.4(f)-341.9(f)-13.1(r)-7(e)-12.5(e)-347.7(r)-7(a)-12.2(d)-9.3(i)-9.9(c)-11.9(a)-12.2(l)-345(s)-7.6(c)-11.9(a)-12.1(v)-7.1(e)-12.5(n)-9.7(g)-10.7(e)-12.5(r)-7(s)-349.1(a)0(n)-21.9(d)-344.4(an)-21.9(ti)-16.6(o)-9.1(x)-14.8(i)-9.9(d)-9.3(a)-12.2(n)-9.7(ts)]TJ T* .0111 Tc [(a)11.1(g)-5.5(ainst)-286.6(l)1.3(ipid)-289.1(pe)11.1(r)-8.5(o)2(xidationme)11.1(d)-10.8(ia)11.1(t)-7.9(e)-1.4(d)-289.1(t)11.1(o)-11.1(x)2.6(icit)11.1(y)-6.4(.)-289(In)-289.5(addition)-289.5(to)]TJ T* 0 Tc [(s)-7.6(m)-10.2(a)-12.2(l)-9.9(l)-307(m)-10.2(o)-9.1(l)-9.9(e)-12.5(c)-11.9(u)-7.7(l)-9.9(e)-12.5(s)-7.6(,)-312.7(a)0(n)-21.9(t)0(i)-16.7(o)-9.1(x)-14.8(i)-9.8(d)-9.3(a)-12.2(n)-9.7(t)-310.3(en)-15.9(z)-12.2(y)-10.7(m)-10.2(e)-12.5(s)-304.8(s)-14(u)-7.7(c)-11.9(h)-306.9(a)-12.2(s)-311.1(h)-9.7(em)-16.4(e)-309.7(o)-9.1(x)-14.8(y)-10.7(g)-10.7(e)0(-)]TJ 0 -1.2266 TD .0121 Tc [(nase-)12.1(1)-6.8(,)-351.2(c).2(at)12.1(a)-6.8(l)2.2(ase,)-351.2(supe)12.1(r)-7.5(o)3(xide)-348.2(di)]TJ 13.8029 0 TD .0099 Tc [(smutase,)-353.4(p)-4.1(e)9.9(r)-9.7(o).8(xi)-6.3(redoxin)-6.1(,)-353.4(and)]TJ ET q 1 i 60.094 732.245 m 298.545 732.245 l 298.545 531.212 l 60.094 531.212 l W n q 238.533 0 0 201.033 60.094 531.212 cm /Im1 Do Q Q BT /F7 1 Tf 8.9663 0 0 8.9663 59.7543 514.4313 Tm 0 Tc [(FIG.)-855.3(1.)-1001.4(Products)-854.1(of)-852.4(lipid)-854.7(peroxidation.)]TJ /F5 1 Tf 21.1059 0 TD [(MDA,)-858.1(mal-)]TJ -21.1059 -1.1128 TD [(ondialdehyde;)-734.1(HNE,)-726.7(4-hydroxy-2-trans-nonenal;)-741.5(acrolein;)]TJ T* [(13-HPODE,)-340(3-hydroperoxy-9Z,11E-octadecadienoic)-345.2(acid;)-337(F)]TJ 6.7246 0 0 5.9768 292.592 493.0014 Tm (2)Tj 8.9663 0 0 8.9663 295.9936 494.4755 Tm (-)Tj -26.3476 -1.1065 TD [(isoprostanes;)-343.7(neuroprostanes.)]TJ ET q 238.533 0 0 108.17 311.131 73.984 cm /Im2 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 319.2377 57.2598 Tm 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[(which)-302.6(f)10.6(u)-10.2(n).9(ctions)-300.5(to)-302(maint)10.6(a)-8.4(in)-302.6(asymmet)10.6(r)-9.5(y)-303.6(o)1.5(f)-299.7(m).4(embrane)-305.4(lipid)]TJ 0 -1.2266 TD .0189 Tc [(b)8.2(i)9(l)9(a)6.7(y)8.2(e)6.4(r)-272.7(\()18.9(46)18.9(\).)]TJ 1.1128 -1.2203 TD 0 Tc [(Although)-267.3(proteins)-260(are)-259.3(the)-263(major)-258.4(targets)-259.7(of)-262.5(HNE)-262.2(reactivity,)]TJ -1.1128 -1.2203 TD [(a)-391.5(great)-397(variety)-388.6(of)-395.3(biomolecules)-392.9(has)-389.9(been)-393.3(identied)-392.8(to)-395.3(form)]TJ 0 -1.2267 TD [(covalent)-370(adducts)-368.3(with)-363.1(HNE,)-366.3(including)-366.9(lipids,)-366.9(nucleic)-364.3(acids,)]TJ 0 -1.2203 TD [(and)-284.1(also)-279(cofactors)-284.8(and)-284.1(vitamins)-281.9(\(39\).)]TJ 1.1128 -1.2203 TD [(Proteins)-196.8(are)-196.1(particularly)-194.9(exposed)-200.1(to)-192.9(modication)-195.9(caused)-194(by)]TJ -1.1128 -1.2266 TD [(HNE,)-322(and)-322(it)-320.1(is)-321(estimated)-321.8(that)-326.3(1%8%)-317.9(of)-319.4(the)-319.9(HNE)-325.4(formed)-320.6(in)]TJ 0 -1.2203 TD [(cells)-241.5(will)-239.9(modify)-239.4(proteins)-241.1(\(101,)-242.2(119\).)-235.9(It)-242.9(is)-238.8(well)-236.2(established)-241.6(that)]TJ T* [(HNE)-357(forms)-356.9(adducts)-355.7(with)-350.5(three)-358.4(different)-353.3(side)-355.5(chains)-358.2(in)-348.4(pro-)]TJ 0 -1.2266 TD [(teins,)-340.3(namely)-330.8(Cys,)-337.6(His,)-330.2(and)-334.7(Lys)-337.5(\(Fig.)-331.9(5\).)-331.7(It)-337.7(can)-331(interact)-336(with)]TJ 0 -1.2203 TD [(thiol)-304.6(\(SH\))-309.2(and)-303.1(amino)-297.6(\(NH)]TJ 6.7246 0 0 5.9768 417.203 121.5496 Tm (2)Tj 8.9663 0 0 8.9663 420.5479 123.0236 Tm [(\))-304(groups)-302.8(of)-300.4(these)-308.5(amino)-303.9(acids)-297.5(via)]TJ -11.9882 -1.2203 TD [(Michael)-267.2(addition)-265.8(resulting)-271.5(in)-266.2(a)-258.7(covalent,)-271.8(bond)-260.2(between)-268.8(HNE)]TJ T* 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[(with)-306.2(altered)-310.5(subunit)-306.7(association.)-304.9(Low)-310.9(levels)-306.1(of)-300.4(HNE)-306.5(modi-)]TJ 28.0042 47.953 TD [(cation)-179.7(appear)-185.7(sufcient)-183.4(to)-180.3(increase)-184.6(susceptibility)-186.5(of)-180.3(proteins)-190.5(to)]TJ 0 -1.2203 TD [(proteolysis)-521.6(and)-511.7(removal)-516.9(by)-521(the)-515.9(proteasomal)-521.6(system.)-513.7(But,)]TJ 0 -1.2266 TD [(while)-195.3(under)-191.7(normal)-190.8(conditions)-200.5(the)-193.4(proteasomal)-199.1(system)-194.7(is)-188.2(able)]TJ 0 -1.2203 TD [(to)-237.2(remove)-248.2(the)-237.7(majority)-241.5(of)-243.5(oxidatively)-244.9(damaged)-240.9(and)-239.9(modied)]TJ T* [(proteins,)-307.2(under)-305.5(severe)-312.3(oxidative)-306.5(stress)-308.5(conditions)-308(accumula-)]TJ 0 -1.2266 TD [(tion)-282(of)-275.1(modied)-284.7(proteins)-279(occurs.)-279.5(This)-283.1(could)-281.8(take)-276.2(place)-281.8(either)]TJ 0 -1.2203 TD [(because)-410.3(of)-414.2(protein)-416.8(cross-linking)-411.4(or)-414.5(malfunction)-413.6(of)-414.2(the)-414.7(pro-)]TJ T* [(teolytic)-406.4(machinery)-410(of)-407.9(the)-414.7(cell.)-407.5(Several)-407.4(other)-411.9(factors)-409.2(besides)]TJ 0 -1.2266 TD [(reactivity)-278.1(may)-279.7(determine)-280.2(the)-282(adduction)-281.9(site,)-280(such)-283.5(as)-272.7(polarity)]TJ 0 -1.2203 TD [(of)-477.5(the)-484.3(microenvironment)-481.2(and)-480.1(accessibility)-485.6(in)-474.8(the)-484.3(tertiary/)]TJ T* [(quaternary)-279.9(structure)-290.1(\(156\).)]TJ 1.1128 -1.2203 TD [(Within)-184.1(this)-192.1(frame,)-190.8(reactivity)-189.6(of)-186.6(HNE)-192.7(towards)-186.4(amyloid)-191.4(beta-)]TJ -1.1128 -1.2266 TD [(peptide)-388.9(\(A)]TJ /F11 1 Tf 4.8117 0 TD (b)Tj /F5 1 Tf .5564 0 TD [(\),)-389.1(the)-389.5(major)-391.2(component)-390.3(of)-388.9(senile)-390.9(plaques)-397.1(\(SPs\),)]TJ -5.3682 -1.2203 TD [(has)-301.4(to)-306.7(be)-307.8(mentioned.)-307.7(Similar)-310.4(to)-300.4(proteins,)-313.5(A)]TJ /F11 1 Tf 19.0573 0 TD (b)Tj /F5 1 Tf .8536 0 TD [(possesses)-307.7(a)-309.3(nu-)]TJ -19.9108 -1.2203 TD [(cleophilic)-197.1(side)-191.1(chain)-198.8(that)-193.5(can)-191.9(react)-195.9(with)-192.4(HNE.)-195.6(HNE)-192.7(covalently)]TJ 0 -1.2266 TD [(modies)-257.7(A)]TJ /F11 1 Tf 4.8181 0 TD (b)Tj /F5 1 Tf .5501 0 TD [(\(140\))-258.2(via)-256.7(1,4-conjugate)-265.1(addition)-259.5(and)-252.5(hastens)-262.2(A)]TJ /F11 1 Tf 20.7455 0 TD (b)Tj /F5 1 Tf -26.1136 -1.2203 TD [(aggregation)-528.9(and)-524.4(toxicity,)-525.4(likely)-525.2(by)-527.3(altering)-527.6(the)-522.2(oligomers)]TJ T* [(formed,)-222.3(which)-232.5(in)-221.9(turn)-227.2(causes)-230.3(oxidative)-224.3(stress)-226.3(that)-231.5(leads)-222.2(to)-230.9(the)]TJ 0 -1.2266 TD [(formation)-302(of)-300.4(even)-301.1(more)-298.1(lipid)-299.5(peroxidation)-307.6(products,)-304(such)-296.2(as)]TJ 0 -1.2203 TD [(HNE)-236.9(and)-239.8(more)-241.2(toxic)-235.8(A)]TJ /F11 1 Tf 10.0092 0 TD (b)Tj /F5 1 Tf .7904 0 TD [(oligomers)-244.1(\(187\).)-236.3(Interestingly,)-245.4(in)-240.9(AD)]TJ -10.7995 -1.2203 TD [(brain)-428.9(the)-427.4(major)-422.8(efux)-430.5(protein)-429.4(for)-433.9(A)]TJ /F11 1 Tf 16.4269 0 TD (b)Tj /F5 1 Tf .5564 0 TD [(,)-426.6(LRP-1,)-428.8(is)-422.2(covalently)]TJ -16.9833 -1.2203 TD [(modied)-430.1(by)-426.2(HNE,)-429.5(and)-429.5(the)-427.4(consequent)-433.5(dysfunction)-434.4(of)-426.9(this)]TJ 0 -1.2266 TD [(efux)-253.5(protein)-252.4(conceivably)-248.4(may)-248.1(contribute)-256.6(to)-249.8(accumulation)-258.2(of)]TJ 0 -1.2203 TD [(this)-280.6(neurotoxic)-288.2(peptide)-281.4(\(144\).)]TJ 1.1128 -1.2203 TD [(Cells)-425.8(are)-423.7(endowed)-430.9(with)-426.3(several)-429.2(mechanisms)-424.1(to)-426.9(detoxify)]TJ -1.1128 -1.2266 TD [(HNE)-363.4(and)-366.3(thereby)-367.3(prevent)-366.9(its)-365.7(potentially)-370.6(damaging)-363.1(actions.)]TJ 0 -1.2203 TD [(GSH)-319.7(is)-321(the)-326.2(most)-324.6(important)-325.9(defense)-324(against)-322(HNE,)-322(and)-322(it)-326.5(has)]TJ T* [(the)-376.8(ability)-379.8(to)-376.3(efciently)-384.6(bind)-374.7(HNE)-376(through)-383.2(its)-378.4(Cys)-379(residue.)]TJ 0 -1.2266 TD [(Also)-363.1(glutathione)-376.8(S-transferases)-367.8(\(GSTs\),)-372.1(participate)-370(and)-366.3(con-)]TJ 0 -1.2203 TD [(tribute)-206.9(to)-205.6(regulate)-205.8(the)-206.1(intracellular)-202.3(level)-209.9(of)-205.6(HNE)-199(together)-208(with)]TJ T* [(the)-294.6(multidrug)-294.1(resistant)-301.5(protein)-296.6(\()-82.7(MRP-1\).)-298.6(The)-297.1(latter)-295.4(catalyzes)]TJ 0 -1.2266 TD [(the)-294.6(export)-298.2(the)-294.6(GSH)-294.4(conjugate)-294.3(of)-294.1(HNE)-293.8(out)-295.5(of)-294.1(neurons.)-300.3(In)-296.4(ad-)]TJ 0 -1.2203 TD [(dition)-307.6(to)-306.7(GSH,)-303.6(the)-307.3(dipeptide)-306.9(carnosine)-311(\()]TJ /F11 1 Tf 17.7294 0 TD (b)Tj /F5 1 Tf .5501 0 TD (-alanyl-L-histidine\))Tj -18.2795 -1.2203 TD [(can)-406.8(quench)-410.1(HNE)-414(via)-408.5(intramolecular)-414.1(Michael)-412.6(addition)-404.9(\(84\).)]TJ T* [(Proteins)-386.5(present)-386.4(in)-380(high)-381.5(amounts)-385.8(within)-382.7(or)-382.8(outside)-385.4(of)-382.6(cells)]TJ 0 -1.2266 TD [(may)-665.4(also)-664.7(play)-666.4(important)-667.4(roles)-665.8(in)-664.5(binding)-670.6(and)-663.5(thereby)]TJ 0 -1.2203 TD [(quenching)-301.3(HNE;)-296.7(examples)-302.4(include)-298.5(albumin)-297.8(\(3\))-297.6(and)-296.7(apolipo-)]TJ T* (protein.)Tj /F3 1 Tf 0 -3.0603 TD [(Lipid)-333.8(Peroxidation)-334.5(and)-338.2(Neurodegenerative)-334.6(Disorders:)]TJ 0 -1.2203 TD [(A)-331.6(Redox)-332.8(Proteomics)-338.8(Overview)]TJ /F5 1 Tf 1.1128 -1.8336 TD .01 Tc [(The)-363(i).1(nvol)-6.2(veme)10(n)-12.3(t)-357.2(of)-363.5(lipid)-359.7(peroxidation)-360.1(in)-360.1(n)-6(e)10(u)-10.2(r)3(od)-5.6(e)10(g)-7(ener-)]TJ -1.1128 -1.2203 TD 0 Tc [(at)-19(i)-9.9(v)-13.4(e)-569(p)-7.7(r)-13.3(o)-9.1(c)-11.9(e)-12.5(s)-7.6(s)-14(es)-576.6(i)-9.9(s)-570.4(w)-14.3(i)-9.9(d)-9.3(e)-12.5(s)-7.6(p)-14(r)-7(e)-12.5(ad)-577.9(\()-13.1(3)0(2)-18(,)-572(16)-18(8)-12.2(\))0(.)-578.8(T)-9.3(h)-9.7(e)-575.3(n)-9.7(u)-7.7(m)-10.2(b)-10.7(e)-12.5(r)-569.8(o)-9.1(f)]TJ T* .0113 Tc [(people)-330(expecte)11.3(d)-339.4(to)-326.6(suffe)11.3(r)-337.1(b).6(ra)11.3(i)-4.4(n)-333.5(disorde)11.3(r)-8.3(smainly)-328.2(AD)-331.5(and)]TJ 0 -1.2266 TD .0103 Tc [(PD)10.3(i)-4.9(s)-598(r)3.3(apidly)-594.8(incre)10.3(a)-8.1(sin)-5.7(g)-588.5(as)-591.7(the)-590.3(w)-4(orld)-5.3(wide)-590.3(populat)10.3(i)-6.3(o)-5.1(n)]TJ 0 -1.2203 TD [(a)10.3(g)-6.3(es.)-466.8(O).9(xidat)10.3(i)-6.3(ve)-463.8(stress)-465.2(occurs)-458.9(in)-461(specic)-463.2(b)-.4(rain)-461(regions)-465.2(a)-1.9(f)10.3(-)]TJ T* 0 Tc [(fe)-19.3(c)-11.9(t)-13.1(ed)-382.3(i)-9.9(n)-376.4(th)-16.5(e)-379.3(r)-7(e)-12.5(s)-7.6(p)-14(e)-12.5(ct)-18.7(i)-9.9(v)-13.4(e)-373(n)-9.7(e)-12.5(u)-7.7(r)-13.3(o)-9.1(d)-9.3(e)-12.5(g)-10.7(e)0(n)-15.9(e)-12.5(r)-13.3(a)0(t)-18.9(i)-9.9(v)-13.4(e)-372.9(d)-9.3(i)-9.8(s)-7.6(o)-15.4(r)-7(d)-9.3(e)-12.5(r)-13.3(s)-374.4(\()0(1)-19(3)0(0)-18(\))-13.1(,)]TJ 0 -1.2267 TD [(an)-21.9(d)-300.2(m)-10.2(e)-12.5(m)-10.2(b)-10.7(r)-7(a)-12.2(n)-9.7(e)-303.4(l)-9.9(i)-16.2(p)-7.7(i)-9.9(d)-306.5(p)-7.7(e)-12.5(r)-7(o)-15.4(x)-8.5(i)-9.9(d)-9.3(a)-12.2(ti)-16.7(o)-15.4(n)-306.9(an)-15.5(d)-306.5(H)-12.6(NE)-312.8(a)-12.2(r)-7(e)-309.7(b)-10.7(el)-16.1(i)-9.8(e)-12.6(v)-13.4(e)0(d)-312.7(t)-13.1(o)]TJ 0 -1.2203 TD .011 Tc [(contribute)-229.2(to)-225.7(neuronal)-226.5(dysf)11(u)-9.8(n)1.3(ct)11(i)-5.6(o)1.9(n)-232.7(a)11(n)-10.9(d)-225.9(dea)11(t)-7.9(h.)-225.9(Howe)11(v)-8.6(e)-1.5(r,)-225.9(the)]TJ T* [(e)11(v)-8.6(idence)-336.7(tha)11(t)-343.1(lipid)-333.4(peroxida)11(t)-8(i)1.1(on)-340.1(is)-338.1(a)-336.3(c)-.9(ruc)11(i)-4.5(al)-334(fact)11(o)-4.9(r)-337.5(is)-338.1(st)11(r)-9.1(o)1.9(n-)]TJ 0 -1.2266 TD .0107 Tc [(ge)10.7(s)-9.5(t)-261.7(for)-261.9(A)-3.3(D,)-264.1(while)-261.1(more)-261.1(d)-5(e)10.7(t)-8.6(a)-1.5(ile)10.7(d)-270.4(s)-3.3(t)10.7(u)-10.1(dies)-262.5(are)-267.4(l).8(a)10.7(c)-7.1(king)-265.6(f)10.7(o)-11.5(r)-261.9(P)3(D,)]TJ 0 -1.2203 TD 0 Tc [(HD)-20.3(,)-268.5(a)-12.2(n)-9.7(d)-274.9(A)-7.7(L)-9.3(S)-11.1(.)-274.8(P)-7.7(r)-13.3(o)-9.1(t)-13.1(eo)-21.6(m)-10.2(i)-9.9(cs)-278.8(a)-12.2(n)-9.7(a)-12.2(l)-9.9(y)-10.7(s)-7.6(i)-9.9(s)-273.2(i)-9.9(s)-273.2(a)-271.4(p)-14(o)-9.1(w)-7.9(e)-12.5(r)-7(f)-13.1(u)-14(l)-269.1(t)-13.1(o)-9.1(o)-9.1(l)-275.4(fo)-15.9(r)-272.6(t)-13.1(h)-9.7(e)]TJ T* .0098 Tc [(ident)9.8(i)-13.2(c)9.8(a)-8(t)-3.3(ion)-366.6(o).7(f)-363.7(p)2.1(uta)9.8(t)-9.2(ive)-369.5(b)-.9(ioma)9.8(r)-9.4(k)-.9(ers)-364.6(o).7(f)-363.7(n)-6.2(e)9.8(u)-10.4(ro)-5.6(de)9.8(g)-7.2(e)-2.7(nerative)]TJ 0 -1.2266 TD .0103 Tc [(diseases,)-372(i).4(n)-5.7(c)10.3(l)-5.2(u)-3.7(ding)-373.5(proteins)-370.4(on)-378.8(which)-372.5(H)-2.3(N)10.3(E)-378.4(adduct)10.3(i)-6.3(o)1.2(n)-378.8(h).6(a)10.3(s)]TJ 0 -1.2203 TD .0106 Tc [(occurred)-618.4(\()10.6(3)-8.4(2)10.6(,)-624.1(168)10.6(\))-8.3(.)-618.3(These)-615.3(m).4(o)-4.8(d)1.3(ica)10.6(t)-8.4(i).7(ons)-616.7(y)-.1(ield)-618.4(a)-614.9(l).7(o)-4.8(s)3(s)-616.7(o)1.5(r)]TJ T* [(reduc)10.6(t)-8.1(ion)-593.5(o)1.5(f)-590.5(e)-1.9(nzyme)-590(a)-1.6(c)10.6(t)-8.1(ivit)10.6(y)-601.3(a)10.6(n)-4.9(d)-593.1(alt)10.6(e)-8.7(ra)10.6(t)-8.3(i).7(ons)-591.4(i).8(n)-593.5(p)-3.4(rotein)]TJ T* .0113 Tc [(str)4.3(u)-2.7(ct)11.3(u)-9.5(r)4.3(e.)-358.3(By)-359.8(using)-359.8(p)3.6(rote)11.3(omics)-363.1(t)11.3(o)-365(i)1.4(nvestiga)11.3(t)-7.6(e)-361.6(t)11.3(h)-5.2(ese)-355.3(p)-2.7(r)4.3(o)2.2(tein)]TJ 0 -1.2266 TD 0 Tc [(c)-11.9(h)-9.7(an)-21.9(ge)-17(s)-14(,)-312.7(s)-7.6(e)-12.5(v)-13.4(e)0(r)-19.6(a)0(l)-325.5(m)-10.2(o)-9.1(l)-9.9(e)-12.5(c)0(u)-19.6(l)-9.9(ar)-322.7(m)-10.2(e)-12.5(c)-11.9(h)-9.7(an)-21.9(i)-9.9(s)-7.6(m)-10.2(s)-317.5(i)-9.9(n)-9.7(v)-7.1(o)-15.4(l)-9.9(v)-7.1(e)-12.5(d)-312.8(i)-9.9(n)-319.5(d)-9.3(e)0(g)-17(e)-12.5(n)-9.7(-)]TJ 0 -1.2203 TD .0105 Tc [(e)10.5(r)-9.1(at)10.5(i)-6.2(o)-4.9(n)-207.9(o)-4.9(f)-211.3(n).8(euronal)-208(c)-1.4(ells)-212.1(have)-217(be)10.5(e)-8.3(n)-214.2(e)10.5(l)-11.9(ucidat)10.5(e)-8.8(d)-213.8(a)10.5(n)-5.1(d)-213.8(l).7(ikely)-208.9(w)-3.8(ill)]TJ T* 0 Tc [(c)-11.9(o)-9.1(n)-9.7(t)-13.1(r)-7(i)-9.9(b)-10.7(u)-7.7(t)-13.1(e)-246.5(to)-249.8(t)-13.1(h)-9.7(e)-246.5(e)0(s)-20.2(t)-13.1(ab)-16.6(l)-9.9(i)-9.9(s)-14(h)-9.7(m)-10.2(e)-12.5(n)-9.7(t)-240.7(o)-9.1(f)-247.1(p)-7.7(r)-13.3(o)-9.1(s)-14(p)-7.7(e)-12.5(c)-11.9(ti)-16.7(v)-13.4(e)-240.2(b)-10.7(i)-9.9(o)-9.1(m)-10.2(a)-12.2(r)-13.3(ke)-17(r)-13.3(s)-241.6(t)-13.1(o)]TJ 0 -1.2267 TD [(b)-10.7(e)-309.7(u)-7.7(s)-14(ed)-319(i)-9.9(n)-313.2(cl)-15.5(i)-16.2(n)-9.7(i)-9.9(c)-11.9(al)-319.2(d)-9.3(i)-9.9(ag)-16.6(n)-16(o)-9.1(s)-7.6(i)-9.9(s)-14(.)]TJ ET q 170.382 0 0 205.852 94.167 526.394 cm /Im4 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 59.7543 509.6125 Tm [(FIG.)-260.9(4.)-1001.5(The)-253.3(rst)-262.7(step)-255.2(of)-258(Michael)-260.5(addition.)]TJ /F5 1 Tf 19.6579 0 TD [(C-3)-259.4(has)-257.1(electron)]TJ -19.6579 -1.1128 TD [(density)-344.8(moved)-339.1(toward)-343.2(O)-338.2(atom)-341.8(of)-338.4(OH)-344.5(on)-341.3(C-4)-341.6(due)-339.4(to)-338.4(induc-)]TJ 0 -1.1065 TD [(tive)-573.7(effect)-575.9(\()]TJ ET q 2.8819 0 0 10.998 108.567 486.425 cm /Im5 Do Q BT 8.9663 0 0 8.9663 111.4582 489.7133 Tm [(\).)-572.5(At)-570.9(the)-579.1(same)-567.4(time,)-573.4(resonance)-579.2(between)-572.3(the)]TJ -5.7665 -1.1128 TD [(double)-312.2(bond)-304.4(between)-313.1(C-3)-303.6(and)-309.4(C-2)-303.6(and)-309.4(the)-307.3(aldehyde)-307.5(dumps)]TJ T* [(electron)-351.4(density)-344.8(away)-346.5(from)-342.9(C-3.)-344.5(The)-341.4(net)-345.2(effect)-348.2(is)-346.3(a)-340.9(partially)]TJ T* [(positive)-247.6(C-3)-240.4(that)-244.1(becomes)-239.1(a)-239.8(target)-245.7(for)-244.2(electrophilic)-242.5(reaction)-243.5(of)]TJ 0 -1.1065 TD [(lone)-338.4(pair)-333.9(of)-332(electrons)-340(on)-334.9(the)-338.9(S)-333.6(atom)-335.4(of)-332(cysteine.)]TJ ET q 238.533 0 0 181.927 60.094 84.019 cm /Im6 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 59.7543 67.2378 Tm [(FIG.)-305.2(5.)-1001.4(Michael)-298.5(addition)-305.2(reaction)-304.5(between)-302.2(HNE)-306.5(and)-296.4(Lys,)]TJ 0 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182.8913 612.9636 Tm (a)Tj 8.9663 0 0 8.9663 218.4377 608.9384 Tm [(Energy)-332(metabolism/)]TJ .999 -1.1065 TD [(mitochondrial)-339.6(function)]TJ 6.7246 0 0 5.9768 318.6141 602.9857 Tm (a)Tj /F11 1 Tf 8.9663 0 0 8.9663 128.0126 589.0392 Tm (a)Tj /F5 1 Tf .4995 0 TD (-enolase)Tj 6.7246 0 0 5.9768 164.5228 593.0077 Tm (a)Tj 8.9663 0 0 8.9663 218.4377 589.0392 Tm [(Energy)-332(metabolism)]TJ 6.7246 0 0 5.9768 295.37 593.0077 Tm (a)Tj 8.9663 0 0 8.9663 59.7543 579.0613 Tm [(EAD)-5468.8(N.A.)-23130.1(SOD2)-7520.4(Antioxidant)-333.5(defense)]TJ /F11 1 Tf 32.8349 -1.1065 TD (a)Tj /F5 1 Tf .4995 0 TD (-enolase)Tj 6.7246 0 0 5.9768 390.6707 573.1085 Tm (a)Tj 8.9663 0 0 8.9663 444.6424 569.14 Tm [(Energy)-332(metabolism)]TJ 6.7246 0 0 5.9768 521.5747 573.1085 Tm (a)Tj 8.9663 0 0 8.9663 354.1605 559.162 Tm [(ATP)-334.5(synthase)]TJ 6.7246 0 0 5.9768 409.0959 563.1306 Tm (a)Tj 8.9663 0 0 8.9663 444.6424 559.162 Tm [(Energy)-332(metabolism/)]TJ .999 -1.1128 TD [(mitochondrial)-339.6(function)]TJ 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[(bition)-283.7(of)-281.5(complete)-283(glycolysis,)-284.4(and)-277.8(ATP)-284(depletion.)]TJ 1.1128 -1.2203 TD [(Similar)-443.1(comments)-451.2(could)-446.2(also)-443.4(be)-446.9(extended)-448(to)-452.2(TCA)-440.8(cycle)]TJ -1.1128 -1.2203 TD [(proteins)-209.4(because)-208(we)-203.9(identied)-209.4(malate)-202.8(dehydrogenase)-209(\()-82.7(MDH\))]TJ 0 -1.2266 TD [(in)-278.8(EAD)-284(and)-284.1(aconitase)-281.6(in)-278.8(LAD)-284(to)-281.5(be)-282.5(HNE-modied.)]TJ 1.1128 -1.2203 TD .0101 Tc [(MDH)-344(c)-1.8(at)10.1(a)-8.9(l).2(yz)10.1(e)-8.3(s)-345.3(t)10.1(h)-12.7(e)-343.9(r)3.1(eversible)-343.9(o)1(x)-4.7(i).2(da)10.1(t)-8.8(i).2(on)-347.4(of)-344.4(mala)10.1(t)-8.8(e)-343.9(t)10.1(o)-353.5(ox)-4.7(-)]TJ -1.1128 -1.2203 TD 0 Tc [(a)-12.2(l)-9.9(o)-9.1(a)-12.2(ce)-18.1(t)-13.1(a)0(t)-18.9(e)-240.2(b)-10.7(y)-232(N)-12.6(A)-14(D)]TJ /F9 1 Tf 6.7246 0 0 5.9768 138.6141 214.696 Tm (+)Tj /F5 1 Tf 8.9663 0 0 8.9663 145.5874 210.7275 Tm .0106 Tc [(in)-226.7(the)-229.6(T)1.3(C)10.6(A)-237.6(c)10.6(y)-5.7(cle.)-226.3(MDH)-229.6(links)-224.7(glycolysis)]TJ -9.32 -1.2267 TD .009 Tc [(t)-4.1(o)-474.3(t)9(h)-7.5(e)-477.8(e)9(l)-7.1(e)-3.5(ct)-4.1(ron)-474.9(t)-4.1(ra)-3.2(ns)-5(por)-4.3(t)-472(cha)-3.2(i)-.9(n)-468.6(b)-1.7(y)-476(t)9(r)-11.1(a)-3.2(nsf)-4.1(e)-3.5(rr)-4.3(ing)-469.6(N)-3.6(A)-5(D)1.3(H)-471.5(t)-4.1(o)]TJ 0 -1.2203 TD 0 Tc [(N)-12.6(A)-7.7(D)-14(H)-543.7(d)-9.3(e)-12.5(h)-9.7(y)-10.7(d)-9.3(r)-13.3(o)-9.1(g)-10.7(en)-22.3(as)-19.8(e)-543.7(\()-13.1(Co)-15.6(m)-10.2(p)-14(l)-9.9(e)-12.5(x)-545.9(I)-8.4(\))-544.2(t)-13.1(h)-9.7(r)-7(o)-15.4(u)-7.7(g)-10.7(h)-547.2(th)-22.8(e)-543.7(m)-10.2(al)-22(at)-19(e)-12.5(-)]TJ T* .0105 Tc [(aspa)10.5(r)-8.7(t)10.5(a)-8.5(t)-2.6(e)-533.2(s)2.9(hut)10.5(t)-9.4(le)-533.2(resulting)-531.4(i).6(n)-530.3(t)-2.6(he)-533.2(produc)10.5(t)-8.2(i).6(on)-530.3(o)-4.9(f)-527.4(ATP.)-536.2(In)]TJ 0 -1.2266 TD .0107 Tc [(contrast)-185.8(to)-181.8(elevate)10.7(d)-194.5(HNE)-188.3(b)10.7(i)-3.6(n)-5.3(d)1.4(ing)-189.7(t)10.7(o)-194.9(M)-.7(DH,)-188.2(M)-.7(DH)-191.6(le)10.7(v)-8.9(e)-1.8(ls)-186.6(were)]TJ 0 -1.2203 TD .0103 Tc [(incr)-3(e)10.3(a)-8.1(sed)-195(i).4(n)-195.4(A)2.6(D)-199.8(p)2.6(at)10.3(i)-6.3(e)-2.2(nt)-2.8(s,)-194.9(bu)-3.7(t)-192.5(t)-2.8(he)-191.9(lev)-3.1(e)10.3(l)-201.8(o)1.2(f)-198.8(p)2.6(r)-3(o)1.2(t)-2.8(e)10.3(i)-5.8(n)-195.4(ox)-4.5(idat)10.3(i)-6.3(o)1.2(n)-195.4(o)-5.1(f)]TJ T* 0 Tc [(M)-11.4(D)-7.7(H)-461.5(w)-14.3(as)-468.7(n)-9.7(o)-15.4(t)-455.7(s)-14(i)-9.9(g)-10.7(n)-9.7(i)-9.9()-9.3(c)-11.9(a)-12.2(n)-9.7(t,)-471.3(w)-7.9(h)-9.7(i)-9.9(c)-11.9(h)-465(p)-7.7(o)-9.1(s)-14(s)-7.6(i)-9.9(b)-10.7(l)-9.9(y)-459.7(r)-13.3(e)-12.5()-9.3(ec)-18.1(t)-13.1(s)-462.9(a)-461.1(c)0(o)-21(m)-10.2(-)]TJ 0 -1.2266 TD .011 Tc [(pe)11(n)-4.9(s)-3(at)11(o)-4.9(r)-2.3(y)-334.9(m).8(e)11(c)-7.1(hanism)-328(in)-333.8(response)-336.7(to)-333.2(oxidative)-336.7(s)3.4(tress)-331.8(\()11(1)-7.9(0)-1.2(7)11(\))-7.9(.)]TJ 0 -1.2203 TD 0 Tc [(A)-14(c)0(t)-18.7(i)-9.9(v)-13.4(i)-9.9(ty)-460.1(o)-9.1(f)-455.7(M)-11.4(D)-7.7(H)-455.2(i)-9.9(n)-9.7(c)-11.9(r)-13.3(e)0(a)-18.4(s)-14(es)-462.8(d)-9.3(u)-7.7(r)-13.3(i)-9.9(n)-9.7(g)-453.3(a)-12.2(g)-10.7(i)-9.9(n)-9.7(g)-453.3(\()0(3)-18.9(0)-12.2(,)-451.8(1)-12.2(41)-18(\),)-465(w)-7.9(h)-9.7(i)-9.9(c)-11.9(h)]TJ T* [(f)-13.1(u)-7.7(r)-13.3(t)0(h)-22.8(e)0(r)-392.6(s)-14(u)-7.7(p)-14(p)-7.7(o)-15.4(r)-7(t)-13.1(s)-387(t)-13.1(h)-9.7(e)-385.6(h)-9.7(y)-10.7(p)-14(o)-9.1(t)-13.1(h)-9.7(es)-20.2(i)-9.9(s)-387(o)-9.1(f)-392.5(m)-10.2(i)-9.9(to)-22.2(ch)-21.6(o)-9.1(n)-9.7(d)-9.3(r)-13.3(i)-9.9(a)0(l)-395.1(d)-9.3(y)-10.7(s)-7.6(f)-13.1(u)-14(n)-9.7(c)-11.9(-)]TJ T* .0123 Tc [(tion)-275.6(in)-275.6(A)4.6(D)-1.7(.)]TJ 1.1128 -1.2266 TD 0 Tc [(Aconitase)-220.2(catalyzes)-222.4(the)-218.7(isomerization)-227.2(of)-218.2(citrate)-218.8(to)-224.5(isocitrate)]TJ -1.1128 -1.2203 TD [(in)-380(the)-376.8(TCA)-377.6(cycle.)-382.4(As)-375.8(an)-382.3(iron-sulfur)-380(protein,)-381.8(its)-378.4(Fe-S)-382.6(cluster)]TJ T* [(participates)-782.3(in)-778.3(the)-775.1(hydrationdehydration)-784.6(reaction)-780.9(that)]TJ 0 -1.2267 TD [(occurs.)-576.7(The)-575.3(three)-573.4(cysteine)-581.3(residues)-573.8(in)-576(the)-579.1(Fe-S)-572.3(core)-578(can)]TJ 27.9978 74.5598 TD [(undergo)-496.1(Michael)-488.5(addition)-493.4(and)-486.4(form)-494.7(acrolein-,)-490.2(HNE-,)-493.2(and)]TJ 0 -1.2203 TD [(MDA-conjugated)-539.6(adducts,)-535.7(thereby)-538(increasing)-537.4(lipid)-533.4(perox-)]TJ 0 -1.2266 TD [(idation)-262.8(markers)-250.7(\(114,)-261.2(188\).)-254.8(Enzymatic)-251(activity)-258.5(of)-256.2(this)-255.3(enzyme)]TJ 0 -1.2203 TD [(is)-358.9(signicantly)-358.6(reduced)-354.9(in)-361(AD,)-353.5(consonant)-357.7(with)-356.8(protein)-359.9(dys-)]TJ T* [(function)-210.7(\(150\).)-198.4(The)-202.3(TCA)-200.6(cycle)-202.4(takes)-201.6(place)-199.6(in)-202.9(the)-199.8(mitochondria;)]TJ 0 -1.2266 TD [(therefore,)-681.3(aconitase)-673.6(impairment)-671.4(results)-672.5(in)-670.8(mitochondrial)]TJ 0 -1.2203 TD [(dysfunction,)-260.3(a)-246.1(common)-249.9(theme)-254.1(of)-249.8(neurodegenerative)-257.4(diseases)]TJ T* [(\(178,)-406.6(212\).)-406.6(As)-407.4(noted)-407.9(above,)-408.6(decreased)-411.2(ATP)-404.1(production)-410.7(can)]TJ 0 -1.2266 TD [(lead)-322.1(to)-325.7(voltage-gated)-322.6(channel)-328.5(and)-315.7(ion-motive)-331.3(pump)-317.8(disrup-)]TJ 0 -1.2203 TD [(tion)-408.5(as)-405.5(well)-400.6(as)-405.5(synapse)-403.2(loss,)-403.9(an)-401.2(early)-406.4(event)-402.7(in)-405.3(Alzheimers)]TJ T* [(disease)-286.7(pathology)-281.9(\(180\).)]TJ 1.1128 -1.2203 TD [(The)-221.3(proteins)-222.1(we)-222.8(identied)-222.1(to)-218.2(be)-219.3(HNE-modied)-218.5(exclusively)]TJ -1.1128 -1.2266 TD [(in)-316.7(MCI)-317.2(included)-320.5(actin,)-312.6(carbonyl)-321.5(reductase)-315.3(\(CR1\),)-317.6(elongation)]TJ 0 -1.2203 TD [(factor)-363.6(Tu)-364.8(\(EF-Tu\),)-363.9(initiation)-359.2(factor)-363.6(1)-359.9(alpha)-361.4(\(eIF-)]TJ /F11 1 Tf 21.2197 0 TD (a)Tj /F5 1 Tf .4995 0 TD [(\),)-357.5(neuropo-)]TJ -21.7192 -1.2203 TD [(lypeptide)-289.4(h3)-281.1(\(Nh3\),)-278.6(and)-284.1(HSP70.)]TJ 1.1128 -1.2266 TD [(Actin)-425.4(is)-422.2(a)-416.8(key)-419.7(protein)-429.4(that)-421.2(plays)-421.1(a)-416.8(central)-424.1(role)-424.2(in)-417.9(main-)]TJ -1.1128 -1.2203 TD [(taining)-252.2(structural)-255.3(integrity,)-251.4(cell)-246.5(morphology,)-254.2(and)-246.2(structure)-252.1(of)]TJ T* [(the)-440(plasma)-432.8(membrane)-432.9(\(18\).)-432.8(In)-435.5(the)-433.7(central)-436.7(nervous)-440.1(system,)]TJ 0 -1.2266 TD [(actin)-322.3(is)-314.7(distributed)-325.2(widely)-319.5(in)-316.7(neurons,)-319.2(astrocytes,)-322.9(and)-315.7(blood)]TJ 0 -1.2203 TD [(vessels.)-327.1(It)-325.1(is)-321(particularly)-321.4(concentrated)-328.2(in)-323.1(growth)-323.2(cones,)-325.7(den-)]TJ T* [(dritic)-282.4(spines,)-279.3(and)-277.8(presynaptic)-287.1(terminals.)-278.4(HNE)-281.2(conjugation)-278.8(of)]TJ T* [(actin)-480.4(can)-470.1(lead)-473.8(to)-477.5(loss)-476.8(of)-471.1(membrane)-477.2(cytoskeletal)-474.8(structure,)]TJ 0 -1.2266 TD [(decreased)-569.2(membrane)-565.7(uidity,)-566(and)-562.3(trafcking)-569.3(of)-566(synaptic)]TJ 0 -1.2203 TD [(proteins)-234.7(and)-220.9(mitochondria.)-231.5(Moreover,)-230.5(actin)-227.5(is)-219.8(involved)-232.6(in)-221.9(the)]TJ T* [(elongation)-358.8(of)-351(the)-351.5(growth)-354.8(cone,)-349.7(and)-353.7(loss)-350.4(of)-357.3(function)-349.8(of)-357.3(actin)]TJ 0 -1.2266 TD [(could)-338.7(play)-331.3(a)-334.6(role)-335.7(in)-329.4(the)-338.9(loss)-331.4(of)-338.4(synapses)-335(and)-334.7(neuronal)-337(com-)]TJ 0 -1.2203 TD [(munication)-286.7(documented)-282.5(in)-285.1(AD)-281(\(128,)-280.1(180\).)]TJ 1.1128 -1.2203 TD .0286 Tc [(CR)5.4(1)-571.6(i)-.2(s)-573.4(a)3.8(n)-575.5(e)3.4(nzy)5.2(m)-.6(e)-572(t)-3.5(hat)-572.5(r)2.6(educes)-573.4(carbonyl-containing)]TJ -1.1128 -1.2266 TD [(compounds)-390.1(t)2.7(o)-391.6(t)-3.6(heir)-395.8(resultant)-389.3(a)]TJ 14.7324 0 TD .0305 Tc [(lc)5.9(ohol)8(s,)-389.7(t)4.7(h)1.8(er)4.5(eb)7.1(y)-391.2(r)4.5(educing)]TJ -14.7324 -1.2203 TD .0278 Tc [(the)-294.6(l)-1(evel)-298.2(of)-295.1(protein)-291.7(c)-3.1(arbo)-6.6(nyls)]TJ 13.6069 0 TD [(.)-291.4(S)-2.4(ubsequ)-5.3(ent)-295.2(m)-1.5(alfunction)-298.1(or)]TJ -13.6069 -1.2203 TD .0284 Tc [(do)-6(wn-regulation)-265.8(o).3(f)-262.9(t)2.6(h)-6.6(i)5.9(s)-263.8(e)-3.1(nzyme)-262.3(w)1.5(o)-6(u)1.8(ld)-259.1(be)-262.3(consistent)-262.9(with)]TJ 0 -1.2266 TD .0268 Tc [(inc)-4.1(r).8(e)-4.7(a)2(s)-6.1(e)1.6(d)-286(p).2(r)-5.5(o)-1.3(te)-4.7(in)-286.4(ca)-4.3(rbonyls)-284.3(i)-2(n)-286.4(A).1(D)-284.4(\()-5.3(92\))-289.8(and)-286(a)-4.3(mne)-4.7(s).2(t)-5.3(i)-2(c)-282.3(M)-3.6(CI)]TJ 0 -1.2203 TD .0287 Tc [(\(167\),)-309.3(which,)-303(because)-312.6(of)-313.2(the)-312.6(p)2.1(olarity)-310.8(o).6(f)-306.9(t)-3.4(he)-306.3(carb)5.3(o)-5.7(n)0(y)5.3(l)-309.9(moi-)]TJ T* .0284 Tc [(ety,)-518.3(could)-518.4(e)3.2(x)-5.4(p)1.8(ose)-521.6(n)-.3(ormally)-519.8(buried)-512(hydrophobic)-514.7(a)-2.7(m)5.5(i)-.4(no)]TJ T* [(aci)5.9(d).1(s)-434.5(t)-3.7(o)-435.9(t)2.6(he)-433.1(protein)-436.6(surface)-439.4(resulting)-437.6(i)-.4(n)-430.2(a)-439(d)6.4(i)-.4(sruption)-436.6(of)]TJ 0 -1.2266 TD .0281 Tc [(conformation.)-316.3(C)-3.7(R)-317.6(h)-.6(as)-321(been)-323(shown)-323(t)2.3(o)-322.4(r)2.1(educe)-319.6(t)-4(he)-319.6(levels)-321(of)]TJ 0 -1.2203 TD .0297 Tc [(HNE)-447.5(\()3.9(5)-1.4(9)4.9(,)-447.4(14)4.9(2\))3.9(.)-453.8(C)4.2(R)-448.7(e)-1.8(xpr)3.7(e)-1.8(ssi)7.2(o)-4.7(n)-447.9(i).9(s)-445.8(a)-1.4(lt)3.9(er)3.7(e)4.5(d)-453.8(in)-447.9(DS)-449.3(and)-447.5(A)3(D)]TJ T* .0271 Tc [(s)-5.8(u).5(bje)-4.4(c)-3.8(ts)-416.8(\(1)-4(5\))-5(.)-412.1(T)-1.2(his)-416.8(e)1.9(nz)-4(yme)-415.4(w).2(a)-4(s)-410.5(f)-5(o)-1(und)-412.2(t)-5(o)-412(b)-2.6(e)-415.4(m)-2.1(odied)-412.2(in)]TJ 0 -1.2266 TD .0286 Tc [(persons)-560.7(w)1.7(ith)-562.8(c)-2.3(orticobasal)-556.6(d).3(eg)]TJ 14.6375 0 TD .0274 Tc [(ene)-4.1(r)1.4(a)-3.7(t)1.6(ion,)-563.6(a)-560.1(n)-1.3(eur)-4.9(o)-.7(logic)-3.5(a)-3.7(l)]TJ -14.6375 -1.2203 TD [(dis)-5.5(o)-.7(rde)-4.1(r)-321.1(who)-7(s).8(e)-326.6(s).8(ymp)-5.6(t)1.6(oms)-328(c)2.8(los)-5.5(e)2.2(ly)-324.8(mirror)-327.4(t)-4.7(hat)-327.2(o)-.7(f)-327.2(P).8(D)-321.8(\()-4.7(48)-3.7(\).)]TJ T* .0281 Tc 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TD .0109 Tc [(polyQ)-567.5(e)10.9(x)-10.1(p)3.2(ansio)-4.5(n)-561.5(can)-561.5(c)-1(ause)-564.4(a)-564(c)-1(onform)10.9(a)-5.1(t)-2.2(ional)-561.7(c)-1(hange)-564.4(i)1(n)]TJ T* 0 Tc [(t)-13.1(h)-9.7(e)-606.9(H)-12.6(tt)-614.3(m)-10.2(u)-7.7(t)-13.1(a)0(n)-21.9(t)-601.1(p)-14(r)-7(o)-9.1(t)-13.1(e)-12.5(i)-9.9(n)-604.1(l)-9.9(e)-12.5(a)0(d)-15.2(i)-16.2(n)-9.7(g)-605.1(to)-610.2(i)-9.9(n)-16(tr)-20.1(an)-21.9(u)-7.7(c)-11.9(l)-9.9(e)-12.5(ar)-613.5(an)-21.9(d)-603.7(i)-9.9(n)-9.7(-)]TJ T* .0109 Tc [(tra)10.9(c)-6.9(yt)10.9(o)-11.3(p)3.2(lasmic)-475.2(ag)10.9(g)-4.3(r)-2.4(eg)10.9(a)-5.7(t)-2.2(e)10.9(s)-9.3(,)-472.6(w)3(hich)-473(are)-475.9(a)-469.1(pa)10.9(t)-8(h)1.2(olo)-4.5(g).2(ic)10.9(a)-6.9(l)-473.2(hall-)]TJ 0 -1.2266 TD .0091 Tc [(ma)-3.1(rk)-336.8(in)-329.4(t)-4(h)-.6(e)-332.2(b)-1.6(ra)-3.1(ins)-333.6(o)0(f)-332.8(b)-1.6(ot)-4(h)-329.4(H)-3.5(D)-333.7(p)1.4(a)-3.1(t)9.1(i)-7.5(e)-3.4(nt)-4(s)-333.7(a)9.1(n)-12.8(d)-329(mou)-4.9(s)1.5(e)-332.2(m)-1.1(ode)-3.4(l)-.8(s)]TJ 0 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[(7.)-501.9(Andersen)-237.2(PM.)-235.1(Genetic)-240.2(factor)-10.3(s)-233.4(i)0(n)-238.3(the)-238.1(early)-237.5(diagnosis)-235.5(of)-235(ALS.)]TJ /F6 1 Tf 1.2519 -1.2385 TD [(Amyotroph)-351.7(Lateral)-358.6(Scler)-351.9(Other)-356.1(Motor)-354.1(Neuron)-353.4(Disord)]TJ /F5 1 Tf 22.548 0 TD [(1)-350.2(Suppl)]TJ -22.548 -1.2318 TD [(1:)-327.9(S3142,)-338.5(2000.)]TJ -1.2519 -1.2385 TD [(8.)-501.9(Andrus)-462.7(PK,)-460.8(Fleck)-454.9(TJ,)-464.2(Gurney)-459.3(ME,)-458.5(and)-459.6(Hall)-465.9(ED.)-458.1(Protein)]TJ 1.2519 -1.2318 TD [(oxidative)-450(d)21.6(a)24.7(m)24.8(a)24.7(g)23.1(e)-429.1(i)26.6(n)-425.5(a)-423.9(t)20.7(r)23.5(a)24.7(n)23(s)21(g)23.1(e)19.4(n)23(i)26.6(c)-426.6(m)24.8(o)18.8(u)23.9(s)27.7(e)-429.1(m)24.8(o)25.5(d)21.6(e)19.4(l)-422(o)18.8(f)-421.1(f)20.7(a)24.7(m)24.8(i)19.9(l)26.6(i)19.9(a)24.7(l)]TJ 0 -1.2385 TD -.0239 Tc [(amyotro)-5.1(p)0(hic)-269.8(l)-4(ate)-4.5(r)-.4(al)-271.8(sclero)-5.1(sis.)]TJ /F6 1 Tf 12.3787 0 TD -.0235 Tc [(J)-270.6(N)-3.3(eurochem)]TJ /F5 1 Tf 5.2152 0 TD -.0247 Tc [(7)-6.7(1)0(:)-270.1(20412)-6.7(048,)-270.1(1998)-6.7(.)]TJ -18.8458 -1.2318 TD 0 Tc [(9.)-501.9(Anzai)-336.1(K,)-344.2(Ogawa)-335.4(K,)-337.5(Goto)-346.6(Y,)-335.9(Senzaki)-342.7(Y,)-335.9(Ozawa)-340.5(T,)-337.7(and)-339.1(Ya-)]TJ 1.2519 -1.2385 TD [(mamoto)-436.5(H.)-434.3(Oxidation-dependent)-443(changes)-439.6(in)-439.1(the)-438.9(stability)]TJ 0 -1.2318 TD [(and)-345.8(permeability)-346.8(of)-342.1(lipid)-350.1(bilayers.)]TJ /F6 1 Tf 15.552 0 TD [(Antioxid)-347.5(Redox)-350.6(Signal)]TJ /F5 1 Tf 9.6807 0 TD (1:)Tj -25.2326 -1.2385 TD [(339347,)-333.8(1999.)]TJ -1.754 -1.2318 TD [(10.)-504(Arendt)-487.5(T.)-491.7(Synaptic)-494.3(degeneration)-493.2(in)-492.7(Alzheimers)-491.6(disease.)]TJ /F6 1 Tf 1.754 -1.2385 TD [(Acta)-333(Neuropathol)]TJ /F5 1 Tf 7.5517 0 TD [(118:)-332.1(167179,)-333.8(2009.)]TJ -9.3058 -1.2318 TD [(11.)-504(Arimura)-335(N,)-340.6(Inagaki)-338.6(N,)-333.9(Chihara)-338.2(K,)-337.5(Menager)-342.4(C,)-334.1(Nakamura)]TJ 1.754 -1.2385 TD [(N,)-400.9(Amano)-404.1(M,)-399.7(Iwamatsu)-408.1(A,)-406(Goshima)-399.9(Y,)-402.9(and)-406.1(Kaibuchi)-404.2(K.)]TJ 0 -1.2318 TD [(Phosphorylation)-430.4(of)-422.4(collapsin)-422.8(response)-432.4(mediator)-422.5(protein-2)]TJ 0 -1.2385 TD [(by)-395.6(Rho-kinase.)-410(Evidence)-402.5(for)-405.6(two)-399.5(separate)-411.8(signaling)-404.9(path-)]TJ 0 -1.2318 TD [(ways)-490.7(for)-499.3(growth)-497.2(cone)-499.3(collapse.)]TJ /F6 1 Tf 15.0231 0 TD [(J)-494.8(Biol)-501.1(Chem)]TJ /F5 1 Tf 5.7106 0 TD [(275:)-499.5(23973)]TJ -20.7337 -1.2385 TD [(23980,)-329.6(2000.)]TJ -1.754 -1.2318 TD [(12.)-504(Atamna)-431(H)-423.2(and)-432.9(Frey)-426.3(WH)-427.5(2nd.)-430.6(Mechanisms)-430.8(of)-429.1(mitochon-)]TJ 1.754 -1.2385 TD [(drial)-573.4(dysfunction)-585.7(and)-580.1(energy)-578(deciency)-584.7(in)-573(Alzheimers)]TJ 0 -1.2318 TD (disease.)Tj /F6 1 Tf 3.7357 0 TD (Mitochondrion)Tj /F5 1 Tf 6.3467 0 TD [(7:)-334.6(297310,)-333.8(2007.)]TJ -11.8364 -1.2385 TD [(13.)-504(Ba)-20.7(de)-19.3(r)-411.7(L)-11.9(a)-8.8(n)-10.4(g)-10.4(e)-409(M)-13.7(L)-11.9(,)-406.1(C)-15(en)-17.8(i)-13.6(n)-10.5(i)-408.6(G)-16.6(,)-406.1(P)-16.2(ir)-16.9(o)-14.7(d)0(d)-17.2(i)-415.3(M,)-419.8(A)-13.3(b)-10.4(du)-14.8(l)-415.3(H)-8.2(M)-13.7(,)-412.8(S)-8.9(u)-9.5(l)-13.6(-)]TJ 1.754 -1.2318 TD [(ta)-21.5(n)-10.4(a)-497.5(R)-10.2(,)-499.8(G)-9.9(a)-8.8(ll)-20.5(i)-495.6(F)-10.4(,)-499.8(M)-13.7(em)-16(o)-503.4(M)0(,)-506.8(a)-8.8(n)-10.4(d)-500.6(B)-11.9(u)-9.5(t)-12.7(t)-12.7(e)0(r)-17.3()-11.9(el)-20.9(d)-500.6(D)0(A)-19.9(.)-499.8(Lo)-19.9(s)-12.5(s)-494.5(o)-14.7(f)]TJ 0 -1.2385 TD .011 Tc [(phospho)-3.7(l)11(i)-9.5(p)1.5(i)11(d)-596.9(asymmet)11(r)-5(y)-588.5(a)2.2(nd)-583.4(el)11(e)-9.9(v)11(a)-11.6(t)11(e)-9.1(d)-583.4(brain)-581.9(a)2.2(p)-5.2(o)3(ptotic)]TJ 0 -1.2318 TD .0116 Tc [(protei)11.6(n)-527.9(l)11.6(e)-9.3(v)11.6(e)-9.5(l)11.6(s)-523.2(i)-2(n)-514.3(s)-.9(ubje)11.6(c)-7.3(t)-1.1(s)-516.4(w)1.1(it)11.6(h)-527.1(a)2.8(mnest)11.6(i)-8(c)-515.4(m)2.9(il)11.6(d)-522.7(c).1(o)-3.1(gni)11.6(t)-8(i)11.6(v)-9(e)]TJ 0 -1.2385 TD 0 Tc [(im)-15.6(p)-16.2(a)-8.8(ir)-16.9(m)-15.4(e)0(n)-17.8(t)-300.6(a)-8.8(n)-10.4(d)-299.8(A)0(l)-20.2(z)-8.8(h)-10.4(e)-14(im)-15.6(e)-14(r)-297.9(d)-11.9(i)0(s)-19.3(e)0(a)-22.8(s)0(e)-19.8(.)]TJ /F6 1 Tf 16.2951 0 TD .011 Tc [(N)11(e)-5.6(urobiol)-288.1(D)-2.3(is)]TJ /F5 1 Tf 6.0923 0 TD .0088 Tc [(29:)-290.2(456)]TJ -22.3874 -1.2385 TD [(464,)-337(2008)-6.7(.)]TJ -1.754 -1.2318 TD 0 Tc [(14.)-504(Bader)-391.4(Lange)-390.3(ML,)-391.5(St)-396.5(Clair)-389(D,)-392.6(Markesbery)-395.3(WR,)-393.7(Studzinski)]TJ 1.754 -1.2385 TD [(CM,)-361.1(Murphy)-358.1(MP,)-362.3(and)-359.2(Butter)-10.7(eld)-359.4(DA.)-359(Age-related)-369.8(loss)-361.1(of)]TJ 0 -1.2318 TD [(phospholipid)-512.2(asymmetry)-511.3(in)-512.7(APP\(NLh\)/APP\(NLh\))-523.4(x)-507.6(PS-)]TJ 0 -1.2385 TD [(1\(P264L\)/PS-1\(P264L\))-776.5(human)-771(double)-770.4(mutant)-772.6(knock-in)]TJ 0 -1.2318 TD [(mice:)-246.4(relevance)-257.5(to)-255(Alzheimer)-253.7(disease.)]TJ /F6 1 Tf 16.583 0 TD [(Neurobiol)-260.4(Dis)]TJ /F5 1 Tf 5.8981 0 TD [(38:)-249.6(104)]TJ -22.4811 -1.2385 TD [(115,)-332.1(2010.)]TJ -1.754 -1.2318 TD [(15.)-504(Ba)-20.7(lc)-18.4(z)-283.3(B)-11.9(,)-278.9(K)-11.7(i)-13.6(r)-10(c)-11.6(h)-10.4(n)-10.5(e)0(r)-291.8(L)-11.9(,)-285.6(C)-8.3(a)-8.8(i)-13.6(r)-10(n)-10.5(s)-280.3(N)-14.9(,)-278.9(F)-10.4(o)-14.7(u)-9.5(n)-10.4(t)-12.7(o)-8(u)-9.5(l)-13.6(a)-8.8(k)-10.4(i)-13.6(s)-280.3(M)-13.7(,)-278.9(a)-15.5(n)-10.5(d)-279.7(L)-11.9(u)-9.5(b)-10.4(e)-14(c)]TJ 1.754 -1.2385 TD [(G)-9.9(.)-707.4(I)-15.1(n)-10.4(cr)-21.5(ea)-16.1(s)-12.5(e)-14(d)-708.2(b)-10.4(r)-10(a)-8.8(i)-13.6(n)-713.4(p)-9.5(r)-10(o)-8(t)-12.7(ei)-20.9(n)-713.4(l)0(e)-20.9(v)0(e)-21.1(l)0(s)-722.3(o)-8(f)-715.7(c)0(a)-20.4(r)-10(b)-10.4(o)-8(n)-10.5(y)-10.4(l)-709.8(r)-10(e)-14(d)-11.9(u)-9.5(c)-11.6(-)]TJ 0 -1.2318 TD .0115 Tc [(t)11.5(a)-10(s)11.5(e)-383.2(and)-375.3(a)2.7(lcohol)-370.3(dehydrogenase)-370.7(in)-373.9(Down)-373.9(syndrome)-370.7(a)-4(n)1.1(d)]TJ 0 -1.2385 TD 0 Tc [(Al)-20.2(z)-8.8(h)-10.5(e)-14(i)0(m)-15.6(e)-14(r)-10()-11.2(s)-367.3(d)-11.9(is)-19.3(e)-14(a)-8.8(s)-12.5(e)0(.)]TJ /F6 1 Tf 9.607 0 TD .0101 Tc [(J)-357.5(N)-3.2(eural)-355.9(T)-1.8(ransm)-358(Suppl)]TJ /F5 1 Tf 10.2497 0 TD .0096 Tc [(\(61\):)-356.3(1)-5.9(93201)-5.9(,)]TJ -19.8567 -1.2318 TD .0088 Tc (2001.)Tj ET q 238.533 0 0 208.63 62.362 523.616 cm /Im7 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 62.022 506.8345 Tm 0 Tc [(FIG.)-387.4(6.)-1001.5(Venn)-380(diagram)-387.2(of)-384.5(HNE)-388.7(modied)-386.7(proteins)-383.9(identi-)]TJ 0 -1.1065 TD [(ed)-422.8(in)-427.1(ALS,)-427.6(AD,)-427.9(and)-422.8(Down)-431(syndrome)-425.5(\(DS\).)]TJ /F5 1 Tf 21.46 0 TD [(ALDO1,)-428.6(al-)]TJ -21.46 -1.1128 TD [(dolase;)-809.6(CR1,)-803.5(carbonyl)-808.4(reductase)-808.4(1;)-799.1(CRMP-2,)-810.5(collapsin)]TJ T* [(response)-516.5(mediator)-513.3(protein-2;)-514.5(EF-Tu,)-514.7(elongation)-516.9(factor)-515.4(Tu;)]TJ T* (eIF-)Tj /F11 1 Tf 1.6756 0 TD (a)Tj /F5 1 Tf .4995 0 TD [(,)-325.4(initiation)-327.6(factor)-325.7(1)-322(alpha;)-326.4(HSP70,)-324.2(heat)-325.7(shock)-327.3(protein70;)]TJ -2.1751 -1.1065 TD [(LDH,)-241.2(lactate)-236.6(dehydrogenase;)-243.5(Nh3,)-239.7(neuropolypeptide)-244.7(h3;)-233.4(NL,)]TJ 0 -1.1128 TD [(neurolament)-578.2(light)-578.1(polypeptide;)-580.9(PGK1,)-574.4(phosphoglycerate)]TJ T* [(kinase)-543.2(1;)-533.6(PK,)-544.5(pyruvate)-539.6(kinase;)-539.8(Prx)-541.7(VI,)-539(peroxiredoxin)-544.3(VI;)]TJ T* [(SOD1,)-321.5(Cu/Zn)-322(superoxide)-319.5(dismutase;)-320.7(SOD2,)-321.5(Mn)-318.3(superoxide)]TJ 0 -1.1065 TD [(dismutase;)-409.2(TPI,)-407.7(triose)-413.4(phosphate)-411.8(isomerase.)-407.8(\(To)-410.9(see)-405.8(this)-413.4(il-)]TJ 0 -1.1128 TD [(lustration)-263.6(in)-266.2(color)-262(the)-263(reader)-262.9(is)-264.1(referred)-264.5(to)-262.5(the)-263(web)-258.9(version)-265.3(of)]TJ T* [(this)-337.5(article)-335.7(at)-335.1(www.liebertpub.com/ars.\))]TJ /F3 1 Tf 0 39.3032 TD (1602)Tj 46.3786 0 TD [(PERLUIGI)-333.4(ET)-338.7(AL.)]TJ ET endstream endobj 170 0 obj <>stream Adobed         s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz?N*S6*ثb͊6*ثb͊6*ثb͊6*ثb͊6*ث48 vִv$_/O\;gKԦ/o4OS; ud39)N`3I{!2?LOgb~D ZП(S?- ؤzGc?yFqPeỰUi"%?gwIН n)>n4tu|AͰ"Ô / 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[(25.)-504(Boyd-Kimball)-302.6(D,)-305.6(Castegna)-306.9(A,)-298.9(Sultan)-10.4(a)-296.7(R)0(,)-302.5(Poon)-310.4(HF,)-304.1(Petroze)]TJ 1.754 -1.2385 TD [(R,)-637.2(Lynn)-645.7(BC,)-640.6(Klein)-645.8(JB,)-638.3(and)-647.1(Buttereld)-644.6(DA.)-640.2(Proteomic)]TJ 0 -1.2318 TD [(identication)-414.4(of)-409(proteins)-418.8(oxidized)-408.6(by)-409(Abeta\(142\))-421.2(in)-405.6(syn-)]TJ 0 -1.2385 TD [(aptosomes:)-340.1(implications)-344.1(for)-345.4(Alzheimers)-344.3(disease.)]TJ /F6 1 Tf 21.9522 0 TD [(Brain)-342.9(Res)]TJ /F5 1 Tf -21.9522 -1.2318 TD [(1044:)-327.5(206215,)-340.5(2005.)]TJ -1.754 -1.2385 TD [(26.)-504(Browne)-433.1(SE)-435.9(and)-432.9(Beal)-436.6(MF.)-436.8(Oxidative)-437.6(damage)-437.5(in)-432.4(Hunting-)]TJ 1.754 -1.2318 TD [(tons)-409.6(disease)-408.6(pathogenesis.)]TJ /F6 1 Tf 12.459 0 TD [(Antioxid)-407.7(Redox)-410.9(Signal)]TJ /F5 1 Tf 9.8681 0 TD [(8:)-401.5(2061)]TJ -22.3271 -1.2385 TD [(2073,)-327.5(2006.)]TJ -1.754 -1.2318 TD [(27.)-504(Browne)-419.7(SE,)-426.9(Bowling)-419.8(AC,)-421(MacGarvey)-428.9(U,)-419.4(Baik)-419.6(MJ,)-425.8(Berger)]TJ 1.754 -1.2385 TD [(SC,)-343(Muqit)-347.8(MM,)-346.4(Bird)-348.7(ED,)-344.3(and)-345.8(Beal)-349.6(MF.)-343.1(Oxidative)-350.6(damage)]TJ 0 -1.2318 TD [(and)-386(metabolic)-389.2(dysfunction)-398.3(in)-385.5(Huntingtons)-397.9(disease:)-393(selec-)]TJ 0 -1.2385 TD [(tive)-315.2(vulnerability)-328.4(of)-322(the)-318.4(basal)-321.8(ganglia.)]TJ /F6 1 Tf 17.152 0 TD [(Ann)-320.3(Neurol)]TJ /F5 1 Tf 5.2621 0 TD [(41:)-316.6(646)]TJ -22.4141 -1.2318 TD [(653,)-332.1(1997.)]TJ -1.754 -1.2385 TD [(28.)-504(Browne)-379.6(SE,)-386.7(Ferrante)-385(RJ,)-388.8(and)-379.3(Beal)-383.1(MF.)-383.3(Oxidative)-390.8(stress)-382.1(in)]TJ 1.754 -1.2318 TD [(Huntingtons)-337.6(disease.)]TJ /F6 1 Tf 9.915 0 TD [(Brain)-336.2(Pathol)]TJ /F5 1 Tf 5.4897 0 TD [(9:)-334.6(147163,)-333.8(1999.)]TJ -17.1587 -1.2385 TD [(29.)-504(Bruening)-398.3(W,)-390.2(Roy)-396.7(J,)-392.1(Giasson)-397(B,)-397.9(Figlewicz)-394.3(DA,)-392.5(Mushynski)]TJ 1.754 -1.2318 TD [(WE,)-482.5(and)-493.1(Durham)-489.3(HD.)-487.8(Up-regulation)-494.7(of)-489.3(protein)-493.4(chaper-)]TJ 0 -1.2385 TD [(ones)-680.9(preserves)-692.7(viability)-686.1(of)-683.5(cells)-687.8(expressing)-688.2(toxic)-687.3(Cu/)]TJ 0 -1.2318 TD [(Zn-superoxide)-443.2(dismutase)-439(mutants)-443.7(associated)-435.7(with)-442.3(amyo-)]TJ 0 -1.2385 TD [(trophic)-336.9(lateral)-335.9(sclerosis.)]TJ /F6 1 Tf 10.7719 0 TD [(J)-334.1(Neurochem)]TJ /F5 1 Tf 5.5835 0 TD [(72:)-330(693699,)-333.8(1999.)]TJ -18.1094 -1.2318 TD [(30.)-504(Bubber)-427.7(P,)-429(Haroutunia)-12.5(n)-425.5(V)0(,)-431.2(Fisch)-433.3(G,)-429.4(Blass)-434.1(JP,)-428.4(and)-432.9(Gibson)]TJ 1.754 -1.2385 TD [(GE.)-822.9(Mitochondrial)-835.8(abnormalities)-827.9(in)-827.4(Alzheimer)-829.5(brain:)]TJ T* [(mechanistic)-335.4(implications.)]TJ /F6 1 Tf 11.4682 0 TD [(Ann)-333.7(Neurol)]TJ /F5 1 Tf 5.2889 0 TD [(57:)-336.7(695703,)-333.8(2005.)]TJ -18.5111 -1.2318 TD [(31.)-504(Busciglio)-626.7(J)-622(and)-620.3(Yankner)-629.9(BA.)-618.8(Apoptosis)-635.1(and)-620.3(increased)]TJ 1.754 -1.2385 TD [(generation)-299.9(of)-295.2(reactive)-299.3(oxygen)-299.7(species)-301.9(in)-291.8(Downs)-300.2(syndrome)]TJ 0 -1.2318 TD [(neurons)-336(in)-332(vitro.)]TJ /F6 1 Tf 7.7459 0 TD (Nature)Tj /F5 1 Tf 3.1867 0 TD [(378:)-338.8(776779,)-333.8(1995.)]TJ -12.6866 -1.2385 TD [(32.)-504(Buttereld)-370.1(DA,)-372.4(Bader)-371.3(Lange)-370.2(ML,)-371.4(and)-365.9(Sultana)-374.1(R.)-369.4(Involve-)]TJ 1.754 -1.2318 TD [(ments)-627.5(of)-623.2(the)-633(lipid)-624.5(peroxidation)-634.9(product,)-626.6(HNE,)-628.5(in)-626.6(the)]TJ 0 -1.2385 TD [(pathogenesis)-377.9(and)-372.6(progression)-386.6(of)-375.5(Alzheimers)-377.8(disease.)]TJ /F6 1 Tf 24.3489 0 TD (Bio-)Tj -24.3489 -1.2318 TD [(chim)-330.2(Biophys)-338.9(Acta)]TJ /F5 1 Tf 8.027 0 TD [(1801:)-334.2(924929,)-333.8(2010.)]TJ -9.7811 -1.2385 TD [(33.)-504(Buttereld)-343.3(DA)-341.2(and)-339.1(Castegna)-340.4(A.)-339(Proteomics)-349.6(for)-338.7(the)-338.5(identi-)]TJ 1.754 -1.2318 TD [(cation)-385(of)-388.9(specically)-392(oxidized)-395.3(proteins)-392(in)-385.5(brain:)-392.3(technol-)]TJ 0 -1.2385 TD [(ogy)-564.3(and)-566.8(application)-568.7(to)-563(the)-566.1(study)-572.5(of)-563(neurodegenerative)]TJ 0 -1.2318 TD (disorders.)Tj /F6 1 Tf 4.6863 0 TD [(Amino)-332.6(Acids)]TJ /F5 1 Tf 5.6973 0 TD [(25:)-336.7(419425,)-333.8(2003.)]TJ 17.5069 77.8202 TD [(34.)-504(Buttereld)-336.6(DA,)-332.3(Galvan)-333.1(V,)-330.8(Lang)-8.1(e)-328.7(MB,)-331.3(Tang)-336.1(H,)-327.2(Sowell)-336.4(RA,)]TJ 1.754 -1.2318 TD [(Spilman)-374.8(P,)-368.8(Fombonne)-374.9(J,)-372(Gorostiza)-380.1(O,)-368.2(Zhang)-371.6(J,)-372(Sultana)-374.1(R,)]TJ 0 -1.2385 TD [(and)-345.8(Bredesen)-353.2(DE.)-344.3(In)-346.9(vivo)-343.6(oxidative)-349.6(stress)-348.7(in)-352.1(brain)-341.1(of)-348.8(Alz-)]TJ 8.4682 0 0 8.4682 329.896 694.4313 Tm [(heimer)-445.7(disease)-448.8(transgenic)-449.2(mice:)-440.6(Requirement)-455.7(for)-445.8(methio-)]TJ T* [(nine)-262.7(35)-265.3(in)-265(amyloid)-262.4(beta-peptide)-271.2(of)-268.4(APP.)]TJ /F6 1 Tf 17.8014 0 TD [(Free)-261.3(Radic)-265(Biol)-266.8(Med)]TJ /F5 1 Tf -17.8014 -1.2318 TD [(48:)-330(136144,)-333.8(2010.)]TJ -1.754 -1.2385 TD [(35.)-504(Buttereld)-430.4(DA,)-432.7(Hensley)-431.2(K,)-431.2(Cole)-425.5(P,)-429(Subramaniam)-434.7(R,)-423(Ak-)]TJ 1.754 -1.2318 TD [(senov)-239.4(M,)-239(Aksenova)-238.4(M,)-239(Bummer)-237(PM,)-241.8(Haley)-235.7(BE,)-235.8(and)-238.7(Carney)]TJ 0 -1.2385 TD [(JM.)-338.8(Oxidatively)-347.7(induced)-337.4(structural)-345.3(alteration)-347(of)-342.1(glutamine)]TJ 0 -1.2318 TD [(synthetase)-332.8(assessed)-326.3(by)-322(analysis)-324.8(of)-328.7(spin)-327.2(label)-321.4(incorporation)]TJ 0 -1.2385 TD [(kinetics:)-364.2(relevance)-364.6(to)-362.2(Alzheimers)-371.1(disease.)]TJ /F6 1 Tf 19.0935 0 TD [(J)-360.9(Neurochem)]TJ /F5 1 Tf 5.6437 0 TD (68:)Tj -24.7372 -1.2318 TD [(24512457,)-331.4(1997.)]TJ -1.754 -1.2385 TD [(36.)-504(Buttereld)-550.9(DA)-548.8(and)-546.7(Lange)-544.3(ML.)-545.5(Multifunctional)-556.1(roles)-546.8(of)]TJ 1.754 -1.2318 TD [(enolase)-409.4(in)-398.9(Alzheimers)-411.3(disease)-401.9(brain:)-405.7(beyond)-406.5(altered)-406.4(glu-)]TJ 0 -1.2385 TD [(cose)-333.9(metabolism.)]TJ /F6 1 Tf 7.8932 0 TD [(J)-340.8(Neurochem)]TJ /F5 1 Tf 5.5901 0 TD [(111:)-332.1(915933,)-333.8(2009.)]TJ -15.2373 -1.2318 TD [(37.)-504(Buttereld)-289.8(DA,)-278.7(Poon)-283.6(HF,)-284(St)-282.7(Clair)-288.6(D,)-278.8(Keller)-284.5(JN,)-286.4(Pierce)-286.9(WM,)]TJ 1.754 -1.2385 TD [(Klein)-364.6(JB,)-370.5(and)-365.9(Markesbery)-368.5(WR.)-366.9(Redox)-364.3(proteomics)-376.3(identi-)]TJ 0 -1.2318 TD [(cation)-567.2(of)-563(oxidatively)-561(modied)-568.8(hippocampal)-567.3(proteins)-566.1(in)]TJ 0 -1.2385 TD [(mild)-375.8(cognitive)-382.5(impairment:)-375.6(insights)-384(into)-379.5(the)-378.7(development)]TJ T* [(of)-335.4(Alzheimers)-337.6(disease.)]TJ /F6 1 Tf 10.5644 0 TD [(Neurobiol)-340.8(Dis)]TJ /F5 1 Tf 6.0655 0 TD [(22:)-330(223232,)-333.8(2006.)]TJ -18.3839 -1.2318 TD [(38.)-504(Buttereld)-309.9(DA,)-305.5(Reed)-304.6(T,)-297.5(Perluigi)-308.4(M,)-305.9(De)-301.8(Marco)-306.4(C,)-300.6(Coccia)-302.8(R,)]TJ 1.754 -1.2385 TD [(Cini)-273.6(C,)-267.1(and)-272.2(Sultana)-266.9(R.)-269(Eleva)-8.5(ted)-266.3(protein-bound)-281.9(levels)-268.9(of)-268.4(the)]TJ 0 -1.2318 TD [(lipid)-403.6(peroxidation)-407.2(product,)-412.4(4-hydroxy-2-nonenal,)-410.1(in)-405.6(brain)]TJ 0 -1.2385 TD [(from)-260.4(persons)-264.4(with)-261.5(mild)-255.3(cognitive)-262(impairment.)]TJ /F6 1 Tf 20.5463 0 TD [(Neurosci)-266.2(Lett)]TJ /F5 1 Tf -20.5463 -1.2318 TD [(397:)-332.1(170173,)-333.8(2006.)]TJ -1.754 -1.2385 TD [(39.)-504(Buttereld)-430.4(DA)-421.6(and)-426.2(Stadtman)-424.5(ER.)-428.2(Protein)-426.4(Oxidation)-428.3(pro-)]TJ 1.754 -1.2318 TD [(cesses)-405.1(in)-405.6(aging)-408.4(brain.)]TJ /F6 1 Tf 10.0957 0 TD [(Adv)-404.3(Cell)-410.7(Aging)-405.7(Gerontol)]TJ /F5 1 Tf 10.9861 0 TD [(2:)-401.5(161191,)]TJ -21.0819 -1.2385 TD (1997.)Tj -1.754 -1.2318 TD [(40.)-504(Cadenas)-242.2(E,)-243.9(Muller)-241.7(A,)-238.6(Brigelius)-242.9(R,)-242.2(Esterbauer)-247.8(H,)-240.2(and)-238.7(Sies)-243.1(H.)]TJ 1.754 -1.2385 TD [(Effects)-409.5(of)-409(4-hydroxynonenal)-411.6(on)-406.7(isolated)-409.7(hepatocytes.)-410.3(Stu-)]TJ 0 -1.2318 TD [(dies)-547.4(on)-547.3(chemiluminescence)-550.4(response,)-550.6(alkane)-548(production)]TJ 0 -1.2385 TD [(and)-332.4(glutathione)-345.2(status.)]TJ /F6 1 Tf 10.5108 0 TD [(Biochem)-336.9(J)]TJ /F5 1 Tf 4.365 0 TD [(214:)-332.1(479487,)-333.8(1983.)]TJ -16.6298 -1.2318 TD [(41.)-504(Calabrese)-589.1(V,)-585.2(Scapagnini)-588(G,)-583.4(Ravagna)-586.7(A,)-586.8(Colombrita)-584.1(C,)]TJ 1.754 -1.2385 TD [(Spadaro)-474.3(F,)-476.7(Buttereld)-483.9(DA,)-472.8(and)-473(Giuffrida)-484.4(Stella)-473.3(AM.)-479.9(In-)]TJ 0 -1.2318 TD [(creased)-611.7(expression)-612.1(of)-609.9(heat)-608.4(shock)-608.5(proteins)-613(in)-613.2(rat)-607.3(brain)]TJ 0 -1.2385 TD [(during)-260(aging:)-258.8(relationship)-257.7(with)-261.5(mitochondrial)-261.8(function)-263.1(and)]TJ 0 -1.2318 TD [(glutathione)-559.4(redox)-551.5(state.)]TJ /F6 1 Tf 11.4615 0 TD [(Mech)-550.3(Ageing)-556.3(Dev)]TJ /F5 1 Tf 8.4689 0 TD [(125:)-553(325335,)]TJ -19.9304 -1.2385 TD (2004.)Tj -1.754 -1.2318 TD [(42.)-504(Campos)-276.8(C,)-273.8(Guzman)-277.1(R,)-275.7(Lopez-Fernandez)-277.7(E,)-277.4(and)-272.2(Casado)-279.2(A.)]TJ 1.754 -1.2385 TD [(Evaluation)-392.3(of)-388.9(urinary)-387.4(biomarkers)-387.5(of)-388.9(oxidative/nitrosative)]TJ 0 -1.2318 TD [(stress)-556.2(in)-559.6(adolescents)-558.5(and)-553.4(adults)-557.8(with)-556.1(Down)-557.8(syndrome.)]TJ /F6 1 Tf 0 -1.2385 TD [(Biochim)-338.1(Biophys)-332.2(Acta)]TJ /F5 1 Tf 9.3459 0 TD [(1812:)-334.2(760768,)-333.8(2011.)]TJ -11.1 -1.2318 TD [(43.)-504(Capone)-454.1(GT.)-454.7(Down)-450.6(syndrome:)-458.5(advances)-453.3(in)-452.5(molecular)-459.3(bi-)]TJ 1.754 -1.2385 TD [(ology)-318(and)-319(the)-318.4(neurosciences.)]TJ /F6 1 Tf 13.0883 0 TD [(J)-320.7(Dev)-313.3(Behav)-318.9(Pediatr)]TJ /F5 1 Tf 8.576 0 TD [(22:)-316.6(4059,)]TJ -21.6643 -1.2318 TD (2001.)Tj -1.754 -1.2385 TD [(44.)-504(Castegna)-327(A,)-319(Aksenov)-323.3(M,)-319.3(Aksenova)-325.5(M,)-326(Thongboonkerd)-328.4(V,)]TJ 1.754 -1.2318 TD [(Klein)-384.7(JB,)-383.9(Pierce)-380.7(WM,)-383.8(Booze)-385.4(R,)-382.8(Markesbery)-381.9(WR,)-380.3(and)-386(But-)]TJ 0 -1.2385 TD [(tereld)-409.6(DA.)-399.2(Proteomic)-410.7(identication)-414.4(of)-402.3(oxidatively)-407(modi-)]TJ 0 -1.2318 TD [(ed)-379.3(proteins)-392(in)-378.8(Alzheimers)-391.2(disease)-388.6(brain.)-378.9(Part)-389.2(I:)-381.1(creatine)]TJ 0 -1.2385 TD [(kinase)-618.7(BB,)-617.4(glutamine)-624(synthase,)-618.4(and)-620.3(ubiquitin)-619.2(carboxy-)]TJ 0 -1.2318 TD 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[(48.)-497.3(Chen)-391.4(ZH,)-397.6(Saito)-393.4(Y,)-389.5(Yoshida)-390(Y,)-389.5(Sekine)-399.4(A,)-385.9(Noguchi)-399.7(N,)-387.5(and)]TJ 1.7473 -1.2385 TD [(Niki)-360.3(E.)-357.8(4-Hydroxynonenal)-362.4(induces)-364.7(adaptive)-354.3(respon)-10.9(se)-354.5(and)]TJ 0 -1.2318 TD [(enhances)-440.4(PC12)-169.4(cell)-434.3(tolerance)-437.9(primarily)-439.6(through)-439.7(induction)]TJ 0 -1.2385 TD [(of)-516.1(thioredoxin)-519.9(reductase)-520.1(1)-510.9(via)-518.2(activation)-515.7(of)-516.1(Nrf2.)]TJ /F6 1 Tf 23.5656 0 TD [(J)-514.9(Biol)]TJ -23.5656 -1.2318 TD (Chem)Tj /F5 1 Tf 2.6578 0 TD [(280:)-332.1(4192141927,)-335.6(2005.)]TJ -4.4052 -1.2385 TD [(49.)-497.3(Cleveland)-523.6(DW)-519.6(and)-519.9(Rothstein)-526.4(JD.)-519.2(From)-519.1(Charcot)-525.1(to)-522.8(Lou)]TJ 1.7473 -1.2318 TD [(Gehrig:)-360.6(deciphering)-370.5(selective)-360.8(motor)-362.1(neuron)-363.7(death)-365.9(in)-358.8(ALS.)]TJ /F6 1 Tf 0 -1.2385 TD [(Nat)-338.9(Rev)-330.2(Neurosci)]TJ /F5 1 Tf 7.6789 0 TD [(2:)-334.6(806819,)-333.8(2001.)]TJ -9.4263 -1.2318 TD [(50.)-497.3(Dalle)-411.4(Donne)-411(I,)-401.1(Scaloni)-409.6(A,)-406(and)-406.1(Buttereld)-410.3(DA.)]TJ /F6 1 Tf 23.0903 0 TD [(Redox)-404.2(Pro-)]TJ -21.343 -1.2385 TD [(teomics:)-242.9(From)-239.4(Protein)-238.4(Modications)-244.4(to)-238.5(Cellular)-246.3(Dysfunction)-239.4(and)]TJ 0 -1.2318 TD (Diseases)Tj /F5 1 Tf 3.4076 0 TD [(.)-332.4(Hoboken,)-341.5(NJ:)-333.3(John)-336.2(Wiley)-336.9(and)-332.4(Sons,)-338.8(2006.)]TJ -5.155 -1.2385 TD [(51.)-497.3(Davies)-457.5(P.)-449.1(Challenging)-452(the)-452.3(cholinergic)-455.1(hypothesis)-462.2(in)-445.8(Alz-)]TJ 1.7473 -1.2318 TD [(heimer)-338.6(disease.)]TJ /F6 1 Tf 7.1299 0 TD (JAMA)Tj /F5 1 Tf 3.0327 0 TD [(281:)-332.1(14331434,)-331.4(1999.)]TJ -11.91 -1.2385 TD [(52.)-497.3(Davis)-289.5(BM,)-284.4(Mohs)-292.3(RC,)-284(Greenwald)-290.7(BS,)-286.3(Mathe)-287.3(AA,)-285.4(Johns)-288.4(CA,)]TJ 1.7473 -1.2318 TD [(Horvath)-379.8(TB,)-369.7(and)-372.6(Davis)-376.5(KL.)-369.5(Clinical)-374.6(studies)-381.3(of)-368.8(the)-378.7(cholin-)]TJ 0 -1.2385 TD [(ergic)-380.9(decit)-383.7(in)-385.5(Alzheimers)-384.5(disease.)-379.6(I.)-381.1(Neurochemical)-389.6(and)]TJ T* [(neuroendocrine)-309.9(studies.)]TJ /F6 1 Tf 10.8456 0 TD [(J)-293.9(A)0(m)-299.5(Geriatr)-298.1(Soc)]TJ /F5 1 Tf 7.2973 0 TD [(33:)-296.5(741748,)-293.7(1985.)]TJ -19.8902 -1.2318 TD [(53.)-497.3(Demicheli)-373.9(V,)-371(Quijano)-372.6(C,)-367.6(Alvarez)-370.1(B,)-371.2(and)-365.9(Radi)-372.5(R.)-369.4(Inactiva-)]TJ 1.7473 -1.2385 TD [(tion)-399.6(and)-392.7(nitration)-401.6(of)-395.6(human)-402.8(superoxide)-396.4(dismutase)-398.8(\(SOD\))]TJ 0 -1.2318 TD [(by)-255(uxes)-261(of)-255(nitric)-259.3(oxide)-253.8(and)-258.8(superoxide.)]TJ /F6 1 Tf 17.8282 0 TD [(Free)-254.6(Radic)-258.3(Biol)-253.4(Med)]TJ /F5 1 Tf -17.8282 -1.2385 TD [(42:)-336.7(13591368,)-331.4(2007.)]TJ -1.7473 -1.2318 TD [(54.)-497.3(Devanand)-299(DP,)-295(Pradhaban)-296.7(G,)-288.8(Liu)-296.1(X,)-289.1(Khandji)-299.9(A,)-292.2(De)-295.1(Santi)-288.8(S,)]TJ 1.7473 -1.2385 TD [(Segal)-276.6(S,)-281.1(Rusinek)-274.7(H,)-280.3(Pelton)-275.8(GH,)-276.9(Honig)-278.1(LS,)-279.6(Mayeux)-276.1(R,)-275.7(Stern)]TJ 0 -1.2318 TD [(Y,)-523.4(Tabert)-529.8(MH,)-521.6(and)-526.6(de)-528.1(Leon)-526.4(MJ.)-519.5(Hippocampal)-531.5(and)-526.6(en-)]TJ 0 -1.2385 TD [(torhinal)-382.1(atrophy)-377.8(in)-372.1(mild)-375.8(cognitive)-375.8(impairment:)-382.3(prediction)]TJ 0 -1.2318 TD [(of)-335.4(Alzheimer)-340.8(disease.)]TJ /F6 1 Tf 9.8748 0 TD (Neurology)Tj /F5 1 Tf 4.5792 0 TD [(68:)-330(828836,)-333.8(2007.)]TJ -16.2014 -1.2385 TD [(55.)-497.3(Dexter)-303.9(D,)-298.9(Carter)-298.2(C,)-293.9(Agid)-296.9(F,)-295.9(Agid)-303.6(Y,)-295.8(Lees)-300.1(AJ,)-291.5(Jenner)-306(P,)-295.1(and)]TJ 1.7473 -1.2318 TD [(Marsden)-523.2(CD.)-521.5(Lipid)-522.5(peroxidation)-527.8(as)-523.4(cause)-518.3(of)-522.8(nigral)-522(cell)]TJ 0 -1.2385 TD [(death)-339.1(in)-332(Parkinsons)-344.9(disease.)]TJ /F6 1 Tf 13.1686 0 TD (Lancet)Tj /F5 1 Tf 2.9926 0 TD [(2:)-334.6(639640,)-333.8(1986.)]TJ -17.9085 -1.2318 TD [(56.)-497.3(Dhitavat)-335.2(S,)-321.3(Rivera)-331.4(ER,)-327.8(Rogers)-326.1(E,)-324.3(and)-332.4(Shea)-323.4(TB.)-329.5(Differential)]TJ 1.7473 -1.2385 TD [(efcacy)-342.1(of)-335.4(lipophilic)-337.8(and)-339.1(cytosolic)-342.8(antioxidants)-336.5(on)-339.8(genera-)]TJ 0 -1.2318 TD [(tion)-419.6(of)-415.7(reactive)-413.1(oxygen)-420.2(species)-415.7(by)-415.7(amyloid-beta.)]TJ /F6 1 Tf 22.3405 0 TD [(J)-414.4(Alzhei-)]TJ -22.3405 -1.2385 TD [(mers)-337.8(Dis)]TJ /F5 1 Tf 4.0236 0 TD [(3:)-334.6(525529,)-333.8(2001.)]TJ -5.7709 -1.2318 TD [(57.)-497.3(Di)-328.1(Domenico)-321.9(F,)-322.7(Sultana)-327.2(R,)-322.5(Tiu)-322.9(GF,)-325.9(Scheff)-324.8(NN,)-328.7(Perluigi)-321.8(M,)]TJ 1.7473 -1.2385 TD [(Cini)-467.7(C,)-461.3(and)-459.6(Butter)-10.7(eld)-459.8(DA.)-466.2(Protein)-466.6(levels)-463(of)-462.6(heat)-467.8(shock)]TJ 0 -1.2318 TD [(proteins)-459(27,)-457.2(32,)-450.5(60,)-457.2(70,)-457.2(90)-452.8(and)-452.9(thioredoxin-1)-461.1(in)-459.2(amnestic)]TJ 0 -1.2385 TD [(mild)-342.4(cognitive)-349(impairment:)-348.8(an)-347.3(investigation)-348.6(on)-346.5(the)-345.2(role)-340.1(of)]TJ 0 -1.2318 TD [(cellular)-523.1(stress)-522.7(response)-519.4(in)-519.4(the)-519.2(progression)-520.5(of)-522.8(Alzheimer)]TJ 0 -1.2385 TD (disease.)Tj /F6 1 Tf 3.7424 0 TD [(Brain)-336.2(Res)]TJ /F5 1 Tf 4.3516 0 TD [(1333:)-334.2(7281,)-336.3(2010.)]TJ -9.8413 -1.2318 TD [(58.)-497.3(Ding)-422.6(Q,)-421.8(Markesbery)-428.7(WR,)-420.5(Cecarini)-425.1(V,)-424.5(and)-426.2(Keller)-425.1(JN.)-420.3(De-)]TJ 1.7473 -1.2385 TD [(creased)-343.9(RNA,)-344(and)-339.1(increased)-347.8(RNA)-339.6(oxidation,)-344.6(in)-338.7(ribosomes)]TJ 0 -1.2318 TD [(from)-280.4(early)-277.7(Alzheimers)-284.1(disease.)]TJ /F6 1 Tf 14.1193 0 TD [(Neurochem)-283.8(Res)]TJ /F5 1 Tf 6.5877 0 TD [(31:)-276.4(705710,)]TJ -20.707 -1.2385 TD (2006.)Tj -1.7473 -1.2318 TD [(59.)-497.3(Do)18.9(or)15.5(n)-365.3(J)0(A)14.1(,)-365.9(M)13.1(a)0(s)18.9(e)0(r)-358.8(E)0(,)-357.8(B)0(l)21.4(u)0(m)-359.7(A)0(,)-359.1(C)0(l)24.9(a)0(f)18.6(f)0(e)13.4(y)-365.2(DJ)20.8(,)-365.9(a)0(n)14.2(d)-366.7(Pe)23.3(te)13.4(rs)17.7(e)12.8(n)-365.3(DR)16.7(.)]TJ 1.7473 -1.2385 TD [(Hu)15.8(ma)22.7(n)-264.8(c)0(a)19.8(r)0(b)19.8(o)0(n)21.7(y)0(l)-251.6(r)0(e)16.2(d)14.9(uc)12.4(t)14(a)0(s)18.9(e)-261.7(ca)19.8(ta)18.6(ly)16.2(ze)24(s)-260.2(r)0(e)16.2(d)0(u)18.7(c)0(t)15.9(i)13.2(on)-252.7(of)-248.3(4-)18.6(ox)20(on)15(on)21.7(-)]TJ 0 -1.2318 TD [(2-)18.6(en)15.7(al)17.8(.)]TJ /F6 1 Tf 3.1599 0 TD [(Bi)17.1(oc)19.5(he)21.4(mi)15.7(st)17.4(ry)]TJ /F5 1 Tf 5.4562 0 TD -.0226 Tc [(4)-22.6(3)0(:)-348.4(1)-22.6(31)-22.6(0)-6.7(6)-22.6(1)-22.6(3)-6.7(1)-22.6(14)-22.6(,)-337.1(2)-22.6(00)-22.6(4)-6.7(.)]TJ -10.3635 -1.2385 TD 0 Tc [(60.)-497.3(Do)18.9(or)15.5(n)-358.6(J)0(A)-354.1(a)0(n)14.2(d)-360(Pe)16.6(t)14(e)0(r)16.2(s)0(e)20.4(n)-365.3(DR)16.7(.)-359.2(C)0(o)17.2(v)13(al)17.8(en)15.7(t)-360.9(a)0(d)19.4(d)0(u)18.7(c)0(t)22.6(i)0(o)18.6(n)-365.3(of)-355.5(nu)20.2(cl)21.7(eo)18.2(-)]TJ 1.7473 -1.2318 TD [(ph)13.5(i)13.2(l)0(i)19.7(c)-326.2(am)22.7(in)16.1(o)-322.6(a)0(c)19.8(i)0(d)21.4(s)-327.1(by)-315.3(4-)18.6(hy)19.4(dr)18.3(ox)20(yn)19.4(on)15.1(e)12.8(n)0(a)20.9(l)-328.2(an)20.9(d)-326.6(4)0(-)18.6(o)0(x)20(o)0(n)21.7(o)0(n)15(e)12.8(na)14.2(l)13.2(.)]TJ /F6 1 Tf 0 -1.2385 TD [(Ch)14.5(em)-311.2(Bi)17.1(ol)-310.6(In)17.1(te)17.4(ra)18.6(ct)]TJ /F5 1 Tf 7.8865 0 TD [(14)22.6(3)15.9(14)22.6(4:)-314.5(93)22.6(1)15.9(00)22.6(,)-325.8(2)0(0)22.6(0)0(3)15.9(.)]TJ -9.6338 -1.2385 TD [(61.)-497.3(Du)-384.3(AT,)-384.4(Schuff)-387.3(N,)-380.8(Amend)-386.5(D,)-379.2(Laakso)-388.4(MP,)-382.4(Hsu)-378.3(YY,)-386.3(Jagust)]TJ 1.7473 -1.2318 TD [(WJ,)-275.8(Yaffe)-279.4(K,)-277.2(Kramer)-284.2(JH,)-273(Reed)-277.8(B,)-277.4(Norman)-281.7(D,)-272.1(Chui)-282.9(HC,)-275.3(and)]TJ 0 -1.2385 TD [(Weiner)-267.1(MW.)-263.3(Magnetic)-269.2(resonance)-267.1(imaging)-263.3(of)-261.7(the)-264.8(entorhinal)]TJ 0 -1.2318 TD [(cortex)-276(and)-272.2(hippocampus)-272.4(in)-271.7(mild)-275.4(cognitive)-268.7(impairmen)-10.4(t)-267.1(and)]TJ 0 -1.2385 TD [(Alzheimers)-331(disease.)]TJ /F6 1 Tf 9.3392 0 TD [(J)-320.7(Neurol)-327.5(Neurosurg)-322(Psychiatry)]TJ /F5 1 Tf 13.0749 0 TD [(71:)-323.3(441)]TJ -22.4141 -1.2318 TD [(447,)-332.1(2001.)]TJ -1.7473 -1.2385 TD [(62.)-497.3(Duan)-350(Z,)-342.6(Lamendola)-350.6(DE,)-344.3(Yusuf)-355.7(RZ,)-346.1(Penson)-346.1(RT,)-347.9(Preffer)-350.8(FI,)]TJ 1.7473 -1.2318 TD [(and)-446.3(Seiden)-447.8(MV.)-451.6(Overexpression)-451.3(of)-449.2(human)-442.9(phosphoglyc-)]TJ 0 -1.2385 TD [(erate)-347.5(kinase)-344.2(1)-343.5(\(PGK1\))-339.9(induces)-351.3(a)-336.8(multidrug)-347.7(resistance)-347.7(phe-)]TJ 0 -1.2318 TD (notype.)Tj /F6 1 Tf 3.6353 0 TD [(Anticancer)-340.4(Res)]TJ /F5 1 Tf 6.5475 0 TD [(22:)-330(19331941,)-338.1(2002.)]TJ -11.9301 -1.2385 TD [(63.)-497.3(Dumont)-283.6(M,)-279.2(Wille)-273.2(E,)-277.4(Stack)-280(C,)-273.8(Calingasan)-286.4(NY,)-277.1(Beal)-276(MF,)-276.1(and)]TJ 1.7473 -1.2318 TD [(Lin)-303.7(MT.)-304.5(Reduction)-309.5(of)-301.9(oxidative)-309.4(stress,)-306.2(amyloid)-302.6(deposition,)]TJ 29.6512 77.8202 TD [(and)-419.5(memory)-421.3(decit)-417.2(by)-422.4(manganese)-426.2(superoxide)-423.2(dismutase)]TJ 0 -1.2318 TD [(overexpression)-249.5(in)-238.3(a)-243.1(transgenic)-241.6(mouse)-246.9(model)-237(of)-241.6(Alzheimers)]TJ 0 -1.2385 TD (disease.)Tj /F6 1 Tf 3.7357 0 TD [(FASEB)-337.5(J)]TJ /F5 1 Tf 4.0236 0 TD [(23:)-336.7(24592466,)-331.4(2009.)]TJ -9.5133 -1.2318 TD [(64.)-504(Duyckaerts)-468(C,)-468(Delato)-10.2(ur)-468.1(B,)-464.9(and)-466.3(Potier)-476.2(MC.)-468.3(Classication)]TJ 1.754 -1.2385 TD [(and)-272.2(basic)-271(pathology)-279.2(of)-268.4(Alzheimer)-273.8(disease.)]TJ /F6 1 Tf 18.8257 0 TD [(Acta)-272.7(Neuropathol)]TJ /F5 1 Tf -18.8257 -1.2318 TD [(118:)-332.1(536,)-334.2(2009.)]TJ 8.4682 0 0 8.4682 317.3102 663.0234 Tm [(65.)-504(Economou)-665.2(A,)-660.4(Papageorgiou)-662.8(SG,)-665.9(Karageorgiou)-665.4(C,)-655.4(and)]TJ 1.754 -1.2318 TD [(Vassilopoulos)-288.9(D.)-285.5(Nonepisodic)-295.3(memory)-287.4(decits)-289(in)-285.1(amnestic)]TJ 0 -1.2385 TD (MCI.)Tj /F6 1 Tf 2.5574 0 TD [(Cogn)-335.5(Behav)-339(Neurol)]TJ /F5 1 Tf 8.3886 0 TD [(20:)-336.7(99106,)-331.7(2007.)]TJ -12.7 -1.2318 TD [(66.)-504(Eismann)-250.5(T,)-243.9(Huber)-252.9(N,)-253.6(Shin)-250.9(T,)-243.9(Kuboki)-251(S,)-254.3(Galloway)-250.9(E,)-243.9(Wyder)]TJ 1.754 -1.2385 TD 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[(65:)-330(21462156,)-338.1(1995.)]TJ -9.6405 -1.2318 TD [(93.)-504(Hensley)-317.4(K,)-324.1(Venkova)-318.1(K,)-324.1(Christov)-323.6(A,)-319(Gunning)-322.4(W,)-316.6(and)-319(Park)]TJ 1.754 -1.2385 TD [(J.)-653.1(Collapsin)-654(response)-660(mediator)-656.8(protein-2:)-659.9(an)-655.3(emerging)]TJ 0 -1.2318 TD [(pathologic)-360.9(feature)-363(and)-359.2(therapeutic)-368(target)-356.6(for)-365.4(neurodisease)]TJ 0 -1.2385 TD (indications.)Tj /F6 1 Tf 5.396 0 TD [(Mol)-331(Neurobiol)]TJ /F5 1 Tf 6.2797 0 TD [(43:)-336.7(180191,)-333.8(2011.)]TJ -13.4297 -1.2385 TD [(94.)-504(Hoyer)-418.7(S.)-421.7(Glucose)-427.2(metabolism)-418.9(and)-426.2(insulin)-425(receptor)-424.6(signal)]TJ 1.754 -1.2318 TD [(transduction)-533.9(in)-526.1(Alzheimer)-534.9(disease.)]TJ /F6 1 Tf 16.5294 0 TD [(Eur)-527.7(J)-534.9(Pharmacol)]TJ /F5 1 Tf 7.699 0 TD (490:)Tj -24.2284 -1.2385 TD [(115125,)-333.8(2004.)]TJ -1.754 -1.2318 TD [(95.)-504(Iannello)-381.9(RC,)-377.7(Crack)-383.8(PJ,)-381.5(de)-380.8(Haan)-377.6(JB,)-383.9(and)-379.3(Kola)-383.5(I.)-381.1(Oxidative)]TJ 1.754 -1.2385 TD [(stress)-315.2(and)-312.4(neural)-314.1(dysfunction)-317.9(in)-311.9(Down)-316.7(syndrome.)]TJ /F6 1 Tf 22.548 0 TD [(J)-307.3(Neural)]TJ -22.548 -1.2318 TD [(Transm)-334.9(Suppl)]TJ /F5 1 Tf 6.1726 0 TD [(57:)-336.7(257267,)-333.8(1999.)]TJ -7.9266 -1.2385 TD [(96.)-504(Ibanez)-429.1(P,)-435.7(Bonnet)-435.8(AM,)-433.1(Debarges)-434.8(B,)-431.4(Lohmann)-437(E,)-438.1(Tison)-431.3(F,)]TJ 1.754 -1.2318 TD [(Pollak)-485.6(P,)-489.3(Agid)-491(Y,)-489.9(Durr)-491.4(A,)-486.3(and)-486.4(Brice)-489.5(A.)-493(Causal)-490(relation)]TJ 0 -1.2385 TD [(between)-655.2(alpha-synuclein)-665.3(gene)-658.1(duplication)-658.8(and)-653.8(familial)]TJ 0 -1.2318 TD [(Parkinsons)-338.2(disease.)]TJ /F6 1 Tf 9.1785 0 TD (Lancet)Tj /F5 1 Tf 2.9859 0 TD [(364:)-332.1(11691171,)-338.1(2004.)]TJ -13.9185 -1.2385 TD [(97.)-504(Inagaki)-311.8(N,)-320.5(Chihara)-318.1(K,)-317.4(Arimura)-314.9(N,)-313.8(Menager)-322.3(C,)-314(Kawano)-319.4(Y,)]TJ 1.754 -1.2318 TD [(Matsuo)-620.9(N,)-628.5(Nishimura)-624.2(T,)-625.5(Amano)-625(M,)-620.6(and)-627(Kaibuchi)-625.2(K.)]TJ 29.6445 77.8202 TD [(CRMP-2)-371.2(induces)-378.1(axons)-373.2(in)-372.1(cultured)-374.1(hippocampal)-373.1(neurons.)]TJ /F6 1 Tf 0 -1.2318 TD [(Nat)-332.2(Neurosci)]TJ /F5 1 Tf 8.4682 0 0 8.4682 378.9353 715.351 Tm [(4:)-334.6(781782,)-333.8(2001.)]TJ -7.545 -1.2385 TD [(98.)-504(Ishihara)-263.7(K,)-263.8(Amano)-263.5(K,)-263.8(Takaki)-264.7(E,)-264(Ebrahim)-261.3(AS,)-260.9(Shimohata)-271.2(A,)]TJ 1.754 -1.2318 TD [(Shibazaki)-368.1(N,)-367.4(Inoue)-371.8(I,)-367.7(Takaki)-371.8(M,)-366.2(Ueda)-369.4(Y,)-362.7(Sago)-370.8(H,)-367.4(Epstein)]TJ 0 -1.2385 TD [(CJ,)-634.7(and)-633.7(Yamakawa)-637.4(K.)-638.7(Increased)-637.3(lipid)-637.9(peroxidation)-641.6(in)]TJ 0 -1.2318 TD [(Downs)-387.3(syndrome)-380.5(mouse)-380.8(models.)]TJ /F6 1 Tf 15.6792 0 TD [(J)-381(Neurochem)]TJ /F5 1 Tf 5.6772 0 TD [(110:)-378.9(1965)]TJ -21.3564 -1.2385 TD [(1976,)-334.2(2009.)]TJ -1.754 -1.2318 TD [(99.)-504(Jouvenceau)-634.6(A,)-633.6(Dutar)-636.8(P,)-629.9(and)-633.7(Billard)-632.3(JM.)-626.6(Alteration)-639.4(of)]TJ 1.754 -1.2385 TD [(NMDA)-336.3(receptor-mediated)-338.9(synaptic)-330.5(respon)-10.9(ses)-326.8(in)-332(CA1)-331.7(area)]TJ 0 -1.2318 TD [(of)-409(the)-412.1(aged)-413.3(rat)-413.1(hippocampus:)-410.6(contributio)-13.3(n)-405.4(o)0(f)-415.7(GABAergic)]TJ 0 -1.2385 TD [(and)-332.4(cholinergic)-341.3(decits.)]TJ /F6 1 Tf 10.879 0 TD (Hippocampus)Tj /F5 1 Tf 5.8646 0 TD [(8:)-334.6(627637,)-333.8(1998.)]TJ -18.9931 -1.2318 TD [(100.)-499.5(Jovanovic)-308.1(SV,)-306.2(Clements)-301.9(D,)-305.6(and)-305.7(MacLeod)-307.5(K.)-297.3(Biomarkers)-308.7(of)]TJ 2.2494 -1.2385 TD [(oxidative)-523.6(stress)-522.7(are)-521.5(signicantly)-528.1(elevated)-524.7(in)-519.4(Down)-524.3(syn-)]TJ 0 -1.2318 TD (drome.)Tj /F6 1 Tf 3.4612 0 TD 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[(156.)-506.2(Poli)-526.7(G)-525.4(and)-533.3(Schaur)-527.9(RJ.)-529.4(4-Hydroxynonenal)-536.5(in)-532.8(the)-532.6(patho-)]TJ 2.2561 -1.2385 TD [(mechanisms)-466(of)-462.6(oxidative)-463.4(stress.)]TJ /F6 1 Tf 14.8758 0 TD [(IUBMB)-465.2(Life)]TJ /F5 1 Tf 5.6437 0 TD [(50:)-463.9(315321,)]TJ -20.5195 -1.2318 TD (2000.)Tj -2.2561 -1.2385 TD [(157.)-506.2(Poon)-364(HF,)-364.4(Calabrese)-368.2(V,)-364.3(Scapagnini)-367.1(G,)-362.4(and)-365.9(Buttereld)-370.1(DA.)]TJ 2.2561 -1.2318 TD [(Free)-316.2(radicals:)-322.7(key)-322.6(to)-322(brain)-321(aging)-321.3(and)-325.7(heme)-321.7(oxygenase)-321.6(as)-322.5(a)]TJ 0 -1.2385 TD [(cellular)-436.1(response)-439.1(to)-435.8(oxidative)-436.6(stress.)]TJ /F6 1 Tf 16.8776 0 TD [(J)-434.5(Gerontol)-443.9(A)-433.5(Biol)-434.1(Sci)]TJ -16.8776 -1.2318 TD [(Med)-333.7(Sci)]TJ /F5 1 Tf 3.7156 0 TD [(59:)-336.7(478493,)-333.8(2004.)]TJ -5.9717 -1.2385 TD [(158.)-506.2(Poon)-504.6(HF,)-504.9(Hensley)-511.5(K,)-504.9(Thongboonkerd)-515.8(V,)-504.9(Merchant)-506.8(ML,)]TJ 2.2561 -1.2318 TD [(Lynn)-244(BC,)-245.6(Pierce)-253.5(WM,)-243.2(Klein)-250.8(JB,)-243.3(Calabrese)-254.4(V,)-243.8(and)-245.4(Buttereld)]TJ 0 -1.2385 TD [(DA.)-539.8(Redox)-551.7(proteomics)-550.4(analysis)-545.8(of)-542.9(oxidatively)-547.6(modied)]TJ 0 -1.2318 TD [(proteins)-465.7(in)-472.6(G93A-SOD1)-468.4(transgenic)-475.9(micea)-462.6(model)-471.3(of)-469.3(fa-)]TJ 0 -1.2385 TD [(milial)-319.5(amyot)-8.4(rophic)-324.2(lateral)-329.2(sclerosis.)]TJ /F6 1 Tf 16.034 0 TD [(Free)-328.2(Radic)-325.3(Biol)-327(Med)]TJ /F5 1 Tf 8.6965 0 TD (39:)Tj -24.7305 -1.2318 TD [(453462,)-333.8(2005.)]TJ -2.2561 -1.2385 TD [(159.)-506.2(Pratico)-382.1(D,)-379.2(Clark)-379.1(CM,)-381.2(Liun)-380.2(F,)-376.3(Rokach)-387.4(J,)-378.7(Lee)-381.4(VY,)-381.1(and)-379.3(Tro-)]TJ 2.2561 -1.2318 TD [(janowski)-568.2(JQ.)-575.1(Increase)-578.5(of)-569.7(brain)-575.4(oxidative)-570.5(stress)-576.3(in)-573(mild)]TJ 0 -1.2385 TD [(cognitive)-503(impairment:)-509.5(a)-504.2(possible)-502.4(predictor)-509.7(of)-502.7(Alzheimer)]TJ 0 -1.2318 TD (disease.)Tj /F6 1 Tf 3.7357 0 TD [(Arch)-334.2(Neurol)]TJ /F5 1 Tf 5.483 0 TD [(59:)-330(972976,)-333.8(2002.)]TJ -11.4749 -1.2385 TD [(160.)-506.2(Pratico)-362(D,)-365.8(Iuliano)-360.2(L,)-364.5(Amerio)-362.1(G,)-362.4(Tang)-362.9(LX,)-367.9(Rokach)-360.6(J,)-365.3(Saba-)]TJ 2.2561 -1.2385 TD [(tino)-406.3(G,)-402.6(and)-406.1(Violi)-408.6(F.)-409.8(Downs)-407.3(syndrome)-407.3(is)-407.6(associated)-415.6(with)]TJ 0 -1.2318 TD [(increased)-649.1(8,12-iso-iPF2)-12.1(alpha-VI)-653.1(levels:)-654.9(evidence)-652.3(for)-653.3(en-)]TJ 0 -1.2385 TD [(hanced)-314.9(lipid)-309.9(peroxidation)-320.2(in)-318.6(vivo.)]TJ /F6 1 Tf 15.4181 0 TD [(Ann)-313.6(Neurol)]TJ /F5 1 Tf 5.2487 0 TD [(48:)-316.6(795798,)]TJ -20.6668 -1.2318 TD (2000.)Tj -2.2561 -1.2385 TD [(161.)-506.2(Pratt)-442.1(DA,)-439.4(Tallman)-444.1(KA,)-444.5(and)-446.3(Porter)-445.9(NA.)-440.9(Free)-443.4(radical)-439.8(oxi-)]TJ 2.2561 -1.2318 TD [(dation)-273(of)-268.4(polyunsaturated)-283(lipids:)-273.2(New)-273.7(mechanistic)-275.2(insights)]TJ 0 -1.2385 TD [(and)-399.4(the)-405.4(development)-411.9(of)-402.3(peroxyl)-405.7(radical)-406.3(clocks.)]TJ /F6 1 Tf 21.7246 0 TD [(Acc)-404.8(Chem)]TJ -21.7246 -1.2318 TD (Res)Tj /F5 1 Tf 1.7674 0 TD [(44:)-336.7(458467,)-333.8(2011.)]TJ -4.0236 -1.2385 TD [(162.)-506.2(Price)-353.2(DL.)-351(New)-354.1(perspectives)-361.9(on)-353.2(Alzheimers)-357.7(disease.)]TJ /F6 1 Tf 25.862 0 TD (Annu)Tj -23.6058 -1.2318 TD [(Rev)-330.2(Neurosci)]TJ /F5 1 Tf 5.8111 0 TD [(9:)-334.6(489512,)-333.8(1986.)]TJ -8.0672 -1.2385 TD [(163.)-506.2(Pryor)-375.9(WA)-372.3(and)-379.3(Porter)-378.9(NA.)-380.7(Suggested)-378.8(mechanisms)-379(for)-378.8(the)]TJ 2.2561 -1.2318 TD [(production)-399.8(of)-395.6(4-hydroxy-2-nonenal)-412.4(from)-394.2(the)-398.7(autoxidation)]TJ 29.6445 77.8202 TD [(of)-355.5(polyunsaturated)-370(fatty)-358.7(acids.)]TJ /F6 1 Tf 14.0524 0 TD [(Free)-361.7(Radic)-358.8(Biol)-360.5(Med)]TJ /F5 1 Tf 8.8237 0 TD [(8:)-354.6(541)]TJ -22.8761 -1.2318 TD [(543,)-332.1(1990.)]TJ -2.2494 -1.2385 TD [(164.)-499.5(Q)-9(i)-13.6(n)-264.9(J)-12.7(,)-272.2(G)-9.9(o)-8(s)-12.5(w)-10.5(a)-8.8(m)-8.7(i)-274.7(R)-10.2(,)-265.5(B)-11.9(a)-8.8(l)-13.6(a)-8.8(b)-10.4(a)-8.8(n)-10.4(o)-14.7(v)-268.2(R)-10.2(,)-265.5(a)-15.5(n)-10.4(d)-266.3(D)-13.3(a)-8.8(w)-10.5(s)-12.5(o)-8(n)-271.5(G)-9.9(.)-272.2(O)-9(x)-12.2(id)-18.8(iz)-22.4(ed)]TJ 8.4682 0 0 8.4682 329.896 694.4313 Tm [(p)-9.5(h)-10.4(o)-14.7(s)0(p)-22(h)-10.4(a)-8.8(t)-12.7(id)-18.8(y)-10.4(l)0(c)-18.4(h)-10.4(o)-14.7(l)0(i)-20.5(n)-10.4(e)-496.1(i)0(s)-508.1(a)-490.8(m)-15.4(a)-8.8(r)-10(k)-10.4(er)-506.1(f)-12.7(o)-8(r)-498.7(n)-10.4(eu)-16.9(r)-10(o)-14.7(in)-17.3()-11.9(a)-8.8(m)-15.4(m)-8.7(a)-8.8(t)-12.7(io)-21.6(n)]TJ T* [(in)-573(m)-8.7(u)-9.5(l)-13.6(t)-12.7(ip)-16.4(l)-13.6(e)-563(s)-12.5(c)0(l)-18.4(e)0(r)-24(o)-8(s)-12.5(i)0(s)-568.3(b)-10.4(r)-10(a)-15.5(in)-17.3(.)]TJ /F6 1 Tf 13.2021 0 TD .01 Tc [(J)-551.7(N)10(e)-13.3(u)-.4(ro)10(s)-11.6(c).9(i)-550.2(R)-.2(es)]TJ /F5 1 Tf 7.1299 0 TD .0088 Tc [(85:)-558(9779)-6.7(84,)]TJ -20.3321 -1.2318 TD [(2007)-6.7(.)]TJ -2.2494 -1.2385 TD 0 Tc [(165.)-499.5(R)-10.2(a)-8.8(k)-10.4(h)-10.4(i)-13.6(t)-253.8(R)-10.2(,)-252.1(C)-8.3(u)-16.2(n)-10.4(n)-10.4(i)0(n)-17.3(g)-10.4(h)-10.4(a)-15.5(m)-249.7(P)-9.5(,)-252.1(F)-10.4(u)-16.2(r)-10(to)-20.7(s)-12.5(-)0(M)-19.7(a)-8.8(t)-12.7(e)0(i)-261.9(A)-13.3(,)-252.1(D)-13.3(a)-8.8(h)-10.5(a)-8.8(n)-251.5(S)-15.6(,)-252.1(Q)-9(i)-254.6(X)-10.2(F)-10.4(,)]TJ 2.2494 -1.2318 TD .5065 Tc [(C)498.2(r)496.5(o)491.8(w).5(J)493.8(P)497(,C)498.2(a)497.7(s)494(h)496.1(m)497.8(a)491(n).6(N)498.3(R)496.3(,K)494.8(o)491.8(n)496.1(d)494.6(e)506.5(j)487.2(e)506.5(w)488.6(s)494(k)496.1(i)-2.5(L)494.6(H)498.3(,a)497.7(n)496(d)-.8(C)491.5(h)496.1(a)497.7(k)496.1(r)496.5(a)497.7(-)]TJ 0 -1.2385 TD .0112 Tc [(bartty)-380.8(A.)-381.5(O)-4.5(x)11.2(i)-7.9(d)-.7(at)11.2(i)-8.4(o)3.2(n-induce)11.2(d)-389.7(m)-4.2(i)11.2(s)-8.1(fold)11.2(i)-7.6(n).8(g)-387.5(a)2.4(nd)-382.3(aggregati)11.2(o)-10.4(n)]TJ 0 -1.2318 TD .0101 Tc [(of)-457.9(supe)-3.9(roxi)10.1(d)-8.7(e)-459.2(di)10.1(s)-9.2(m)1.4(utase)-452.5(a)-5.4(nd)-450.4(i)-3.5(t)-2.6(s)-457.6(i)10.1(m)-5.5(p).6(l)-3.5(i)10.1(c)-8.3(a)1.3(ti)-3.5(ons)-457.6(f)-2.6(or)-455.1(am)-5.3(yo-)]TJ 0 -1.2385 TD 0 Tc [(t)-12.7(r)-10(o)-8(p)-9.5(h)-10.4(i)-13.6(c)-580.6(l)-13.6(a)-8.8(t)-12.7(er)-17.3(a)-8.8(l)-582.6(s)-12.5(c)-11.5(le)-20.9(r)-10(o)-8(s)-12.5(i)-13.6(s.)]TJ /F6 1 Tf 11.7293 0 TD .5818 Tc [(JB)581.8(i)565.4(o)570.3(l)-5.1(C)571.6(h)573(e)571.8(m)]TJ /F5 1 Tf 6.032 0 TD .0088 Tc [(277)-6.7(:)-571.4(4755)-6.7(1475)-6.7(56,)]TJ -17.7613 -1.2318 TD [(2002)-6.7(.)]TJ -2.2494 -1.2385 TD 0 Tc [(166.)-499.5(Rapoport)-297.7(SI.)-289.5(In)-293.4(vivo)-296.8(PET)-294.5(imaging)-290.1(and)-299(postmortem)-299(studies)]TJ 2.2494 -1.2318 TD [(suggest)-590.8(potentially)-589.3(reversible)-594.4(and)-586.8(irreversible)-591.2(stages)-586.4(of)]TJ 0 -1.2385 TD [(brain)-501.7(metabolic)-503(failure)-504(in)-499.3(Alzheimers)-505(disease.)]TJ /F6 1 Tf 21.9321 0 TD [(Eur)-500.9(Arch)]TJ -21.9321 -1.2318 TD [(Psychiatry)-337.2(Clin)-337.5(Neurosci)]TJ /F5 1 Tf 10.6648 0 TD [(249)-334.4(Suppl)-338.9(3:)-334.6(4655,)-336.3(1999.)]TJ -12.9142 -1.2385 TD [(167.)-499.5(Reed)-277.8(T,)-277.4(Perluigi)-274.9(M,)-279.2(Sultana)-280.3(R,)-275.7(Pierce)-280.2(WM,)-270(Klein)-284.3(JB,)-276.8(Turner)]TJ 2.2494 -1.2318 TD [(DM,)-272.4(Coccia)-269.3(R,)-269(Markesbery)-274.7(WR,)-266.5(and)-272.2(Buttereld)-269.7(DA.)-272(Redox)]TJ 0 -1.2385 TD [(proteomic)-464.3(identication)-468(of)-455.9(4-hydroxy-2-nonena)-17.2(l-modied)]TJ T* [(brain)-394.6(proteins)-392(in)-392.2(amnestic)-393.6(mild)-395.9(cognitive)-389.2(impairmen)-10.3(t:)-385.4(in-)]TJ 0 -1.2318 TD [(sight)-354.2(into)-359.4(the)-358.6(role)-353.5(of)-362.1(lipid)-350.1(peroxidation)-367.1(in)-352.1(the)-358.6(progression)]TJ 0 -1.2385 TD [(and)-339.1(pathogenesis)-351.1(of)-342.1(Alzheimers)-351(disease.)]TJ /F6 1 Tf 18.6584 0 TD [(Neurobiol)-340.8(Dis)]TJ /F5 1 Tf 6.0789 0 TD (30:)Tj -24.7372 -1.2318 TD [(107120,)-333.8(2008.)]TJ -2.2494 -1.2385 TD [(168.)-499.5(Reed)-471.9(TT.)-470.1(Lipid)-475.6(peroxidation)-474.2(and)-473(neurodegenerative)-487.6(dis-)]TJ 2.2494 -1.2318 TD (ease.)Tj /F6 1 Tf 2.4369 0 TD [(Free)-334.9(Radic)-338.7(Biol)-333.7(Med)]TJ /F5 1 Tf 8.73 0 TD [(51:)-336.7(13021319,)-331.4(2011.)]TJ -13.4163 -1.2385 TD [(169.)-499.5(R)-10.2(e)-14(ed)-534.8(T)-11.9(T)0(,)-531.8(P)-16.2(ie)-20.9(r)-10(c)0(e)-534.4(W)-10.9(M)-13.7(,)-526.6(Ma)-15.8(r)-10(k)-10.4(e)-14(s)-12.5(b)-10.4(e)0(r)-17.3(y)-525.9(W)-10.9(R)-10.2(,)-526.6(a)-8.8(n)-10.5(d)-527.4(B)-11.9(u)-9.5(t)-12.7(t)-12.7(e)0(r)-17.3()-11.9(e)-14(l)0(d)]TJ 2.2494 -1.2318 TD .0125 Tc [(DA)12.5(.)-467.1(P)3(ro)4.5(teo)4.5(m)3.8(ic)-454.3(ide)12.5(n)-5.3(ti)12.5(c)-4.3(atio)4.5(n)-459.9(o)4.5(f)-462.2(H)4.3(NE)12.5(-bo)4.5(u)-3.7(nd)-454.7(prote)12.5(i)-8.4(ns)-455.2(in)]TJ 0 -1.2385 TD 0 Tc [(ea)-22.8(r)-10(l)0(y)-546.1(A)-13.3(lz)-22.4(h)-10.5(e)0(i)-20.9(m)-8.7(er)-546.2(d)-11.9(i)-13.6(se)-19.8(a)-8.8(s)-12.5(e:)-547.3(i)-13.6(n)-10.4(s)-12.5(i)0(g)-17.2(h)-10.4(t)-12.7(s)-541.4(in)-17.3(t)-12.7(o)-536.9(t)-12.7(h)-10.4(e)-542.9(r)-10(o)-8(l)-13.6(e)-536.2(o)-14.7(f)-534.9(l)-13.6(ip)-16.4(i)-13.6(d)]TJ 0 -1.2318 TD .0114 Tc [(peroxi)11.4(d)-7.4(a)2.6(tion)-266.8(in)-266.8(the)-270.4(p)1.9(rogre)11.4(s)-8.4(si)11.4(o)-10.1(n)-266.8(of)-269.1(AD.)]TJ /F6 1 Tf 17.5872 0 TD .0108 Tc [(Brai)10.8(n)-278.5(R).6(es)]TJ /F5 1 Tf 4.3047 0 TD .0088 Tc [(1)-6.7(274:)-270.1(66)-6.7()]TJ -21.8919 -1.2385 TD [(76,)-337(2009)-6.7(.)]TJ -2.2494 -1.2318 TD 0 Tc [(170.)-499.5(Roberts)-372.3(LJ)-366.1(2nd,)-363.6(Montine)-377.5(TJ,)-363.8(Markesbery)-368.5(WR,)-373.6(Tapper)-365.1(AR,)]TJ 2.2494 -1.2385 TD [(Hardy)-343.8(P,)-348.7(Chemtob)-347.1(S,)-341.3(Dettbarn)-353.5(WD,)-343.3(and)-345.8(Morrow)-348(JD.)-345.1(For-)]TJ 0 -1.2318 TD [(mation)-323.4(of)-328.7(isoprostane-like)-331.6(compounds)-331.1(\(neuroprostanes\))-336.6(in)]TJ 0 -1.2385 TD [(vivo)-437.4(from)-434.4(docosahexaenoic)-438.2(acid.)]TJ /F6 1 Tf 15.2708 0 TD [(J)-434.5(Biol)-434.1(Chem)]TJ /F5 1 Tf 5.5299 0 TD [(273:)-432.5(13605)]TJ -20.8007 -1.2318 TD [(13612,)-336.3(1998.)]TJ -2.2494 -1.2385 TD [(171.)-499.5(Roper)-560.5(RJ)-558.5(and)-560.1(Reeves)-560.5(RH.)-558.3(Understanding)-565.5(the)-566.1(basis)-559.8(for)]TJ 2.2494 -1.2318 TD [(Down)-336.8(syndrome)-333.6(phenotypes.)]TJ /F6 1 Tf 13.49 0 TD [(PLoS)-338.8(Genet)]TJ /F5 1 Tf 5.1818 0 TD [(2:)-327.9(e50,)-337.3(2006.)]TJ -20.9212 -1.2385 TD [(172.)-499.5(R)-10.2(o)-8(s)-12.5(s)-12.5(o)-8(r)-425.1(M)-13.7(N)-8.2(,)-426.2(I)-15.1(v)0(e)-21.1(r)-10(se)-19.8(n)-425.5(L)-11.9(L)-11.9(,)-419.5(J)-12.7(o)-14.7(h)-10.5(n)-10.4(so)-20.4(n)-425.5(A)-13.3(J,)-432.2(M)-13.7(o)-8(u)-9.5(n)-10.5(t)-12.7(j)-12(o)-8(y)-425.4(C)-15(Q)-9(,)-426.2(a)-8.8(n)-10.4(d)]TJ 2.2494 -1.2318 TD .011 Tc [(Roth)-648.8(M)11(.)-649.8(Ch)-6.1(ol)11(i)-9.5(n).6(ergi)11(c)-650.1(d)-.9(e)11(c)-5.8(i)-2.6(t)-644.4(i)11(n)-649(f)-1.7(rontal)-638.6(cere)11(b)-6.7(r)1(a)-4.5(l)-638.6(corte)11(x)]TJ 0 -1.2385 TD 0 Tc [(in)-445.8(A)-13.3(l)0(z)-15.7(h)-17.1(ei)-20.9(m)-8.7(e)0(r)-17.3()-11.2(s)-440.9(d)0(i)-18.8(s)-12.5(ea)-16.1(s)-12.5(e)-435.8(i)-13.6(s)-434.2(a)-8.8(g)-10.4(e)-435.8(d)-11.9(e)-14(p)-9.5(en)-24.5(de)-19.3(n)-10.4(t)-12.7(.)]TJ /F6 1 Tf 19.3546 0 TD .0102 Tc (Lancet)Tj /F5 1 Tf 3.1465 0 TD .0088 Tc [(2:)-424.1(14)-6.7(22,)]TJ -22.5012 -1.2318 TD [(1981)-6.7(.)]TJ -2.2494 -1.2385 TD 0 Tc [(173.)-499.5(Rozzini)-341.2(L,)-337.7(Chilovi)-342.3(BV,)-342.7(Conti)-341(M,)-339.4(Bertoletti)-344.2(E,)-337.7(Delrio)-346.9(I,)-334.2(Tra-)]TJ 2.2494 -1.2318 TD [(bucchi)-401.8(M,)-393(and)-399.4(Padovani)-399.5(A.)-399.3(Conversion)-403.6(of)-395.6(amnestic)-400.3(Mild)]TJ 0 -1.2385 TD [(Cognitive)-493.1(Impairment)-493.3(to)-489.3(dementia)-495.9(of)-489.4(Alzheimer)-494.8(type)-488.5(is)]TJ 0 -1.2318 TD [(independent)-541.5(to)-529.5(memory)-535.1(deterioration.)]TJ /F6 1 Tf 18.1496 0 TD [(Int)-531.3(J)-534.9(Geriatr)-532.4(Psy-)]TJ -18.1496 -1.2385 TD (chiatry)Tj /F5 1 Tf 3.1532 0 TD [(22:)-336.7(12171222,)-331.4(2007.)]TJ -5.4027 -1.2318 TD [(174.)-499.5(Rubinsztein)-347.1(DC,)-340.7(Leggo)-349.2(J,)-338.5(Coles)-344.3(R,)-342.6(Almqvist)-346.2(E,)-344.4(Biancalana)]TJ 2.2494 -1.2385 TD [(V,)-317.4(Cassiman)-317.9(JJ,)-317.8(Chotai)-316.3(K,)-317.4(Connarty)-320.1(M,)-312.6(Crauford)-320.3(D,)-319(Curtis)]TJ 0 -1.2318 TD [(A,)-365.8(Curtis)-367.9(D,)-365.8(Davidson)-373.4(MJ,)-365.5(Differ)-370.9(AM,)-366.1(Dode)-368.6(C,)-367.6(Dodge)-372.2(A,)]TJ 0 -1.2385 TD [(Frontali)-475.8(M,)-473.3(Ranen)-475.7(NG,)-471(Stine)-474.8(OC,)-470.3(Sherr)-475.1(M,)-473.3(Abbott)-475.9(MH,)]TJ 0 -1.2318 TD [(Franz)-403.2(ML,)-411.6(Graham)-404.8(CA,)-407.6(Harper)-408.6(PS,)-404.4(Hedreen)-410.7(JC,)-407.1(Hayden)]TJ 0 -1.2385 TD (MR,)Tj /F6 1 Tf 2.2361 0 TD [(et)-377.6(al.)]TJ /F5 1 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[(xynonenal,)-497.7(a)-497.5(key)-496.7(molecule)-501.4(in)-492.7(stress)-502.6(mediated)-497.4(signaling.)]TJ /F6 1 Tf 0 -1.2318 TD [(Acta)-333(Biochim)-338.1(Pol)]TJ /F5 1 Tf 7.458 0 TD [(50:)-330(319336,)-333.8(2003.)]TJ -9.7141 -1.2385 TD [(212.)-506.2(Yarian)-510.4(CS,)-510.4(Rebrin)-517.1(I,)-508.3(and)-513.2(Sohal)-511.6(RS.)-512.2(Aconitase)-520(and)-513.2(ATP)]TJ 2.2561 -1.2318 TD [(synthase)-339.5(are)-340.8(targets)-342.2(of)-335.4(malondialdehyde)-344.2(modication)-340.1(and)]TJ 0 -1.2385 TD [(undergo)-308.6(an)-307.1(age-related)-311.8(decrease)-311.1(in)-305.2(activity)-311.3(in)-305.2(mouse)-313.8(heart)]TJ T* (mitochondria.)Tj /F6 1 Tf 6.5877 0 TD [(Biochem)-430.7(Biophys)-425.9(Res)-431.9(Commun)]TJ /F5 1 Tf 13.4699 0 TD [(330:)-425.8(151156,)]TJ -20.0576 -1.2318 TD (2005.)Tj -2.2561 -1.2385 TD [(213.)-506.2(Yehuda)-453.2(S,)-455.1(Rabinovitz)-458.3(S,)-455.1(Carasso)-457.2(RL,)-455(and)-452.9(Mostofsky)-462.3(DI.)]TJ 2.2561 -1.2318 TD [(The)-518.4(role)-514.2(of)-522.8(polyunsaturated)-524(fatty)-519.3(acids)-520.3(in)-519.4(restoring)-523.4(the)]TJ 0 -1.2385 TD [(aging)-522.2(neuronal)-533.4(membrane.)]TJ /F6 1 Tf 12.8942 0 TD [(Neurobiol)-528.2(Aging)]TJ /F5 1 Tf 7.5651 0 TD [(23:)-524.1(843853,)]TJ -20.4593 -1.2318 TD (2002.)Tj -2.2561 -1.2385 TD [(214.)-506.2(Yoshida)-369.9(H,)-374.1(Watanabe)-372.8(A,)-372.5(and)-365.9(Ihara)-374.5(Y.)-369.4(Collapsin)-379.5(response)]TJ 2.2561 -1.2318 TD [(mediator)-449.3(protein-2)-461.4(is)-454.5(associated)-455.8(with)-455.7(neurobrillary)-455.4(tan-)]TJ 0 -1.2385 TD [(gles)-499(in)-499.3(Alzheimers)-498.3(disease.)]TJ /F6 1 Tf 13.2624 0 TD [(J)-494.8(Biol)-501.1(Chem)]TJ /F5 1 Tf 5.7173 0 TD [(273:)-499.5(97619768,)]TJ -18.9797 -1.2318 TD (1998.)Tj -2.2561 -1.2385 TD [(215.)-506.2(Zana)-312.7(M,)-319.3(Janka)-319(Z,)-315.8(and)-319.1(Kalman)-316.5(J.)-318.4(Oxidative)-317.1(stress:)-319.6(a)-316.8(bridge)]TJ 2.2561 -1.2318 TD [(between)-347.3(Downs)-347.1(syndrome)-347(and)-345.8(Alzheimers)-351(disease.)]TJ /F6 1 Tf 23.9472 0 TD (Neu-)Tj -23.9472 -1.2385 TD [(robiol)-333.9(Aging)]TJ /F5 1 Tf 5.4696 0 TD [(28:)-330(648676,)-333.8(2007.)]TJ -7.7258 -1.2318 TD [(216.)-506.2(Zarkovic)-782.5(K.)-786(4-hydroxynonenal)-793.2(and)-787.7(neurodegenerative)]TJ 2.2561 -1.2385 TD (diseases.)Tj /F6 1 Tf 4.1508 0 TD [(Mol)-337.7(Aspects)-340.1(Med)]TJ /F5 1 Tf 7.5785 0 TD [(24:)-330(293303,)-333.8(2003.)]TJ -13.9854 -1.2318 TD [(217.)-506.2(Zhu)-371.6(M,)-372.9(Qin)-374.4(ZJ,)-375.4(Hu)-379.2(D,)-372.5(Munishkina)-381.1(LA,)-371.1(and)-379.3(Fink)-372.8(AL.)-371.1(Al-)]TJ 2.2561 -1.2385 TD [(pha-synuclein)-482.3(can)-486(function)-484(as)-483.2(an)-474.5(antioxidant)-491.4(preventing)]TJ 0 -1.2318 TD [(oxidation)-387.1(of)-388.9(unsaturated)-395.5(lipid)-390.2(in)-385.5(vesicles.)]TJ /F6 1 Tf 19.1069 0 TD (Biochemistry)Tj /F5 1 Tf 5.6236 0 TD (45:)Tj -24.7305 -1.2385 TD [(81358142,)-331.4(2006.)]TJ 8.9663 0 0 8.9663 188.2204 307.5023 Tm [(Address)-339.4(correspondence)-340.1(to:)]TJ /F6 1 Tf 4.1225 -1.2203 TD [(Dr.)-333.8(Marzia)-340.7(Perluigi)]TJ -6.4241 -1.2266 TD [(Department)-337.8(of)-336.3(Biochemical)-335(Sciences)]TJ .3225 -1.2203 TD [(Faculty)-337.4(of)-330(Pharmacy)-336.5(and)-338.3(Medicine)]TJ 2.4343 -1.2203 TD [(Sapienza)-337.6(University)-340(of)-330(Rome)]TJ 4.5019 -1.2267 TD [(P.le)-337.3(Aldo)-332.3(Moro,)-336.1(5)]TJ 2.2889 -1.2203 TD [(00185)-332.7(Rome)]TJ 3.2437 -1.2203 TD (Italy)Tj -13.98 -2.5039 TD (E-mail:)Tj /F5 1 Tf 3.2626 0 TD (marzia.perluigi@uniroma1.it)Tj -14.1001 -2.6367 TD [(Date)-292.1(of)-287.8(rst)-290(submission)-286.1(to)-287.8(ARS)-288.6(Central,)-288.8(November)-290.5(14,)-286.5(2011;)]TJ 0 -1.2203 TD [(date)-293.7(of)-294.1(nal)-294(revised)-293.6(submission,)-301.6(November)-290.5(21,)-292.8(2011;)-291.8(date)-293.7(of)]TJ 0 -1.2266 TD [(acceptance,)-289.3(November)-277.9(23,)-280.1(2011.)]TJ /F3 1 Tf 36.6729 62.0214 TD [(Abbreviations)-331.2(used)]TJ /F5 1 Tf 8.4682 0 0 8.4682 323.2062 705.4865 Tm (13-HPODE)Tj /F14 1 Tf 5.0613 0 TD ()Tj /F5 1 Tf .9373 0 TD [(3-hydroperoxy-9Z,11E-octadecadienoic)-351.7(acid)]TJ -2.4302 -1.2385 TD (A)Tj /F11 1 Tf .7766 0 TD (b)Tj /F14 1 Tf .7163 0 TD ()Tj /F5 1 Tf .9373 0 TD [(amyloid)-336(beta-peptide)]TJ -2.6444 -1.2385 TD (AA)Tj /F14 1 Tf 1.7072 0 TD ()Tj /F5 1 Tf .9373 0 TD [(arachidonic)-339.6(acid)]TJ -2.6444 -1.2318 TD (AD)Tj /F14 1 Tf 1.7072 0 TD ()Tj /F5 1 Tf .9373 0 TD [(Alzheimer)-340.8(disease)]TJ -4.5324 -1.2385 TD (ALDO1)Tj /F14 1 Tf 3.5951 0 TD ()Tj /F5 1 Tf .9373 0 TD (aldolase)Tj -2.9993 -1.2318 TD (ALS)Tj /F14 1 Tf 2.062 0 TD ()Tj /F5 1 Tf .9373 0 TD [(amyotrophic)-339.3(lateral)-335.9(sclerosis)]TJ -3.0662 -1.2385 TD (APP)Tj /F14 1 Tf 2.1289 0 TD ()Tj /F5 1 Tf .9373 0 TD [(amyloid)-336(precursor)-336.1(protein)]TJ -2.9792 -1.2318 TD (CR1)Tj /F14 1 Tf 2.0419 0 TD ()Tj /F5 1 Tf .9373 0 TD [(carbonyl)-337.5(reductase)-339.4(1)]TJ -4.8336 -1.2385 TD (CRMP-2)Tj /F14 1 Tf 3.8964 0 TD ()Tj /F5 1 Tf .9373 0 TD [(collapsin)-335.8(response)-338.6(med)-7.9(iator)-334.3(protein-2)]TJ -3.4679 -1.2318 TD (DHA)Tj /F14 1 Tf 2.5306 0 TD ()Tj /F5 1 Tf .9373 0 TD [(docosahexanoic)-343.9(acid)]TJ -2.3967 -1.2385 TD (DS)Tj /F14 1 Tf 1.4595 0 TD ()Tj /F5 1 Tf .9373 0 TD [(Down)-336.8(syndrome)]TJ -3.2537 -1.2318 TD (EAD)Tj /F14 1 Tf 2.3164 0 TD ()Tj /F5 1 Tf .9373 0 TD [(early)-337.9(Alzheimer)-334.1(disease)]TJ -3.7826 -1.2385 TD (EF-Tu)Tj /F14 1 Tf 2.8453 0 TD ()Tj /F5 1 Tf .9373 0 TD [(elongation)-337.6(factor)-338.3(Tu)]TJ -3.2804 -1.2318 TD (eIF-)Tj /F11 1 Tf 1.6737 0 TD (a)Tj /F14 1 Tf .6695 0 TD ()Tj /F5 1 Tf .9373 0 TD [(initiation)-338.4(factor)-338.3(1)-330.2(alpha)]TJ -3.0194 -1.2385 TD (ETC)Tj /F14 1 Tf 2.0821 0 TD ()Tj /F5 1 Tf .9373 0 TD [(electron)-342(transport)-335.7(chain)]TJ -4.2713 -1.2318 TD (F)Tj 5.9275 0 0 5.9275 342.4818 547.2565 Tm (2)Tj 8.4682 0 0 8.4682 345.9401 548.5605 Tm (-IsoP)Tj /F14 1 Tf 2.3766 0 TD ()Tj /F5 1 Tf .9373 0 TD (F)Tj 5.9275 0 0 5.9275 378.6519 547.2565 Tm (2)Tj 8.4682 0 0 8.4682 384.9448 548.5605 Tm (isoprostane)Tj -5.0947 -1.2385 TD (F)Tj 5.9275 0 0 5.9275 346.4503 536.8251 Tm (4)Tj 8.4682 0 0 8.4682 349.9086 538.0723 Tm (-NP)Tj /F14 1 Tf 1.908 0 TD ()Tj /F5 1 Tf .9373 0 TD (F)Tj 5.9275 0 0 5.9275 378.6519 536.8251 Tm (4)Tj 8.4682 0 0 8.4682 382.1668 538.0723 Tm (-neuroprostane)Tj -4.2847 -1.2318 TD (fALS)Tj /F14 1 Tf 2.3833 0 TD ()Tj /F5 1 Tf .9373 0 TD [(familial)-334.4(amyotrophic)-339.3(lateral)-335.9(sclerosis)]TJ -2.3833 -1.2385 TD (GS)Tj /F14 1 Tf 1.4461 0 TD ()Tj /F5 1 Tf .9373 0 TD [(glutamine)-336.1(synthase)]TJ -3.2068 -1.2318 TD (GSH)Tj /F14 1 Tf 2.2695 0 TD ()Tj /F5 1 Tf .9373 0 TD (glutathione)Tj -2.9926 -1.2385 TD (GST)Tj /F14 1 Tf 2.0553 0 TD ()Tj /F5 1 Tf .9373 0 TD [(glutathione)-338.5(S-transferase)]TJ -2.698 -1.2318 TD (HD)Tj /F14 1 Tf 1.7607 0 TD ()Tj /F5 1 Tf .9373 0 TD [(Huntington)-340.7(disease)]TJ -3.3541 -1.2385 TD (HNE)Tj /F14 1 Tf 2.4168 0 TD ()Tj /F5 1 Tf .9373 0 TD 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.9373 0 TD [(mass)-337(spectrometry)]TJ -4.2311 -1.2385 TD (NDGA)Tj /F14 1 Tf 3.2938 0 TD ()Tj /F5 1 Tf .9373 0 TD [(nordihydroguaiaretic)-344.8(acid)]TJ -3.9566 -1.2318 TD (NF-)Tj /F11 1 Tf 1.6938 0 TD (j)Tj /F5 1 Tf .5557 0 TD (B)Tj /F14 1 Tf .7699 0 TD ()Tj /F5 1 Tf .9373 0 TD [(nuclear)-339(factor-kappa)-337.8(B)]TJ -3.0863 -1.2385 TD (NFT)Tj /F14 1 Tf 2.149 0 TD ()Tj /F5 1 Tf .9373 0 TD [(neurobrillary)-341.6(tangle)]TJ -2.9993 -1.2385 TD (Nh3)Tj /F14 1 Tf 2.062 0 TD ()Tj /F5 1 Tf .9373 0 TD [(neuropolypeptide)-346.2(h3)]TJ -4.4052 -1.2318 TD (NMDA)Tj /F14 1 Tf 3.4679 0 TD ()Tj /F5 1 Tf .9373 0 TD [(N-methyl)-338.5(D-aspartic)-341.1(acid)]TJ -2.852 -1.2385 TD (O)Tj 5.9275 0 0 5.9275 356.4283 317.1401 Tm (2)Tj /F14 1 Tf .0861 .7365 TD ()Tj /F10 1 Tf .7652 0 TD ($)Tj /F14 1 Tf 8.4682 0 0 8.4682 366.066 318.3873 Tm ()Tj /F5 1 Tf .9373 0 TD (superoxide)Tj -3.9499 -1.2318 TD (PCAD)Tj /F14 1 Tf 3.0127 0 TD ()Tj /F5 1 Tf .9373 0 TD [(preclinical)-337.7(Alzheimer)-340.8(disease)]TJ 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