A Peptide That Binds Specifically to the β-Amyloid of Alzheimers Disease Selection and Assessment of Anti-β-Amyloid Neurotoxic Effects 英文参考文献.docVIP
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APeptideThatBindsSpecificallytotheb-Amyloidof
Alzheimer’sDisease:SelectionandAssessmentof
Anti-b-AmyloidNeurotoxicEffects
FangWang1,Xian-LingZhou1,Qi-GangYang1,Wen-HuaXu1,FeiWang1,Yong-PingChen2,
Gui-HaiChen1*
1Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China, 2Department of Biomedical Engineering,
JohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica
Abstract
The accumulation of the amyloid-b peptide (Ab) into amyloid plaques, an essential event in Alzheimer’s disease (AD)
pathogenesis,hascausedresearcherstoseekcompoundsthatphysiologicallybindAbandmodulateitsaggregationand
neurotoxicity.InordertodevelopnewAb-specificpeptidesforAD,arandomized12-merpeptidelibrarywithAb1-10asthe
targetwasusedtoidentifypeptidesinthepresentstudy.Afterthreeroundsofselection,specificphageswerescreened,
andtheirbindingaffinitiestoAb1-10werefoundtobehighlyspecific.Finally,aspecialpeptidewassynthesizedaccordingto
thesequencesoftheselectedphages.Inaddition,theeffectsofthespecialpeptideonAbaggregationandAb-mediated
neurotoxicityinvitroandinvivowereassessed.Theresultsshowthatthespecialpeptidenotonlyinhibitedtheaggregation
of Ab into plaques, but it also alleviated Ab-induced PC12 cell viability and apoptosis at appropriate concentrations as
assessed by the cell counting kit-8 assay and propidium iodide staining. Moreover, the special peptide exhibited a
protectiveeffectagainstAb-inducedlearningandmemorydeficitsinrats,asdeterminedbytheMorriswatermazetask.In
conclusion,weselectedapeptidethatspecificallybindsAb1-10andcanmodulateAbaggregationandAb-inducedneuronal
damage.ThisopensuppossibilitiesforthedevelopmentofanoveltherapeuticapproachforthetreatmentofAD.
Citation:WangF,ZhouX-L,YangQ-G,XuW-H,WangF,etal.(2011)APeptideThatBindsSpecificallytotheb-AmyloidofAlzheimer’sDisease:Selectionand
AssessmentofAnti-b-AmyloidNeurotoxicEffects.PLoSONE6(11):e27649.doi:10.1371/journal.pone.0027649
Editor:MaximAntopolsky,UniversityofHelsi
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