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1、DOI:10.1002/cbic.200900474CopperTransferfromCu–AbtoHumanSerumAlbuminInhibitsAggregation,RadicalProductionandReducesAbToxicity[a,b][c,d][c,d][a,b]LorenaPerrone,EmmanuelleMothes,MaevaVignes,AnaïsMockel,[c,d][a,e,f][a,b]CindyFigueroa,Marie-ChristineMiquel,Mari
2、e-LiseMaddelein,and[c,d]PeterFaller*Amyloid-bpeptides(Ab)andtheproteinhumanserumalbu-andstoichiometrically,2)HSAandDAHKwereabletodecreasemin(HSA)interactinvivo.TheyarebothlocalisedinthebloodCu-inducedaggregationofAb,3)HSAandDAHKsuppressedplasmaandinthecereb
3、rospinalfluid.Amongotherfunctions,thecatalyticHOCproductioninvitroandROSproductioninHSAisinvolvedinthetransportoftheessentialmetalcopper.neuroblastomacellsgeneratedbyCu–Abandascorbate,ComplexesbetweenAbandcopperionshavebeenproposed4)HSAandDAHKwereabletoresc
4、uethesecellsfromthetox-tobeanaberrantinteractionimplicatedinthedevelopmentoficityofCu–Abwithascorbate,5)DAHKwasmorepotentinAlzheimer’sdisease,whereCuisinvolvedinAbaggregationROSsuppressionandrestorationofneuroblastomacellviabilityIIandproductionofreactiveox
5、ygenspecies(ROS).Inthepres-thanHSA,incorrelationwithaneasierreductionofCu–HSAentwork,westudiedcopper-exchangereactionbetweenAbthanCu–DAHKbyascorbate,invitro.OurdatasuggestthatIIandHSAorthetetrapeptideDAHK(N-terminalCu-bindingHSAisabletodecreaseaberrantCu–Ab
6、interaction.Thereper-domainofHSA)andtheconsequenceofthisexchangeonAb-cussionofthecompetitionbetweenHSAandAbtobindCuininducedROSproductionandcelltoxicity.ThefollowingresultsthebloodandbrainanditsrelationtoAlzheimer’sdiseaseareIIwereobtained:1)HSAandDAHKremov
7、edCufromAbrapidlydiscussed.IntroductionExtracellularamyloidplaquesandintracellularneurofibrillaryclearthattheaminoacidsHis6,-13,-14andAsp1areinvolvedtanglesarethetwomainmorphologicalhallmarksofAlzheim-inCubindingaroundneutralpH(forrecentpublicationssee[1–3]
8、er’sdisease(AD).Amyloidplaquescontainaggregatedrefs.[21]and[22];forrecentreviewseeref.[15]).Inagreementformsofthe39–43aminoacidamyloid-bpeptide(Ab).AbiswiththeproductionofROSbyAbandcellulartoxicityofAb
