Alzheimer’s-Related Peptide Amyloid-β Plays a Conserved Role in Angiogenesis 英文参考文献.docVIP

Alzheimer’s-RelatedPeptideAmyloid-bPlaysa ConservedRoleinAngiogenesis D.JoshuaCameron1,2,CooperGalvin1,TursunAlkam1,3,HarpreetSidhu1,JohnEllison1, SalvadoreLuna1,3,DouglasW.Ethell1,3,4 * 1Molecular Neurobiology, WesternUniversityofHealth Sciences, Pomona, California, UnitedStates ofAmerica, 2CollegeofOptometry,WesternUniversityofHealth Sciences, Pomona, California, United States of America, 3Graduate College ofBiomedical Sciences, Western University of Health Sciences, Pomona, California, United StatesofAmerica,4CollegeofOsteopathicMedicineofthePacific,WesternUniversityofHealthSciences,Pomona,California,UnitedStatesofAmerica Abstract Alzheimer’s disease research has been at an impasse in recent years with lingering questions about the involvement of Amyloid-b (Ab). Early versions of the amyloid hypothesis considered Ab something of an undesirable byproduct of APP processingthatwreakshavoconthehumanneocortex,yetevolutionaryconservation-overthreehundredmillionyears- indicates this peptide plays an important biological role in survival and reproductive fitness. Here we describe how Ab regulatesbloodvesselbranchingintissuesasvariedashumanumbilicalveinandzebrafishhindbrain.Highphysiological concentrationsofAbmonomerinducedangiogenesisbyaconservedmechanismthatblocksc-secretaseprocessingofa Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize c-secretase activity, which may have significant implications for our understandingofAlzheimer’spathogenesisvis-a`-vis vascularchangesthatsetthestageforensuingneurodegeneration. Citation:CameronDJ,GalvinC,AlkamT,SidhuH,EllisonJ,etal.(2012)Alzheimer’s-RelatedPeptideAmyloid-bPlaysaConservedRoleinAngiogenesis.PLoS ONE7(7):e39598.doi:10.1371/journal.pone.0039598 Editor:JonathanMatsui,PomonaCollege,UnitedStatesofAmerica ReceivedFebruary13,2012;AcceptedMay24,2012;PublishedJuly9,2012 Copyright: ? 2012 Cameron et al. This is an open