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Aβ Internalization by Neurons and Glia英文文献资料.doc

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Aβ Internalization by Neurons and Glia英文文献资料

SAGE-HindawiAccesstoResearch InternationalJournalofAlzheimer’sDisease Volume2011,ArticleID127984,17pages doi:10.4061/2011/127984 ReviewArticle AβInternalizationbyNeuronsandGlia AmanyMohamedandElenaPossedeChaves DepartmentofPharmacology,UniversityofAlberta,Edmonton,AB,CanadaT6G2H7 CorrespondenceshouldbeaddressedtoElenaPossedeChaves,elena.chaves@ualberta.ca Received23October2010;Accepted23December2010 AcademicEditor:AnneEckert Copyright?2011A.MohamedandE.PossedeChaves.ThisisanopenaccessarticledistributedundertheCreativeCommons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. In the brain, the amyloid β peptide (Aβ) exists extracellularly and inside neurons. The intracellular accumulation of Aβ in Alzheimer’s disease brain has been questioned for a long time. However, there is now su?cient strong evidence indicating thataccumulationofAβinsideneuronsplaysanimportantroleinthepathogenesisofAlzheimer’sdisease.IntraneuronalAβ originates from intracellular cleavage of APP and from Aβ internalization from the extracellular milieu. We discuss here the di?erentmolecularmechanismsthatareresponsibleforAβinternalizationinneuronsandthelinksbetweenAβinternalization andneuronaldysfunctionanddeath.AbriefdescriptionofAβuptakebygliaisalsopresented. 1.Introduction “intraneuronalAβhypothesis”doesnotargueagainstarole forextracellularAβbutcomplementsthetraditionalamyloid cascadehypothesis[6–8]. Alzheimer’sdisease(AD)isthemostcommonformofage- relateddementiaintheelderly.Theincreaseoftheaverage age of the population is causing a signi?cant rise in the numberofpeoplea?ictedwiththisdevastatingdisease,and itispredictedthattheincidenceofADwillapproximately triplicateby2040[1]ifmoree?ectivetherapeuticstrategies arenotmadeavailable.Inordertodevelopbettertherapeutic approaches,themolecularpathwaysleadingtothepatholog- icalalterationsofthediseasemustbefullyunderstood. Major neuropathological and neurochemical hallmarks