Amyloid-β Peptide Binds to Cytochrome C Oxidase Subunit 1 英文参考文献.docVIP

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Amyloid-β Peptide Binds to Cytochrome C Oxidase Subunit 1 英文参考文献.doc

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Amyloid-β Peptide Binds to Cytochrome C Oxidase Subunit 1 英文参考文献

Amyloid-bPeptideBindstoCytochromeCOxidase Subunit1 LuisFernandoHernandez-Zimbron1,JoseLuna-Mun?oz2,RaulMena2,RicardoVazquez-Ramirez1, CarlosKubli-Garfias1,DavidH.Cribbs3,4,KarenManoutcharian1,GoarGevorkian1* 1Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico DF, Mexico, 2Department of Neurosciences, CINVESTAV-IPN, Mexico DF, Mexico, 3Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America, 4DepartmentofNeurology,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Extracellular and intraneuronal accumulation of amyloid-beta aggregates has been demonstrated to be involved in the pathogenesisofAlzheimer’sdisease(AD).However,theprecisemechanismofamyloid-betaneurotoxicityisnotcompletely understood.Previousstudiessuggestthatbindingofamyloid-betatoanumberofmacromoleculeshasdeleteriouseffects on cellular functions. Mitochondria were found to be the target for amyloid-beta, and mitochondrial dysfunction is well documentedinAD.InthepresentstudywehaveshownforthefirsttimethatAb1–42boundtoapeptidecomprisingthe amino-terminalregionofcytochromecoxidasesubunit1.Phageclone,selectedafterscreeningofahumanbraincDNA libraryexpressedonM13phageandbearinga61aminoacidfragmentofcytochromecoxidasesubunit1,boundtoAb1– 42 in ELISA as well as to Ab aggregates present in AD brain. Ab 1–42 and cytochrome c oxidase subunit 1 co- immunoprecipitated from mitochondrial fraction of differentiated human neuroblastoma cells. Likewise, molecular dynamicssimulationofthecytochromecoxidasesubunit1andtheAb1–42peptidecomplexresultedinareliablehelix- helixinteraction,supportingtheexperimentalresults.TheinteractionbetweenAb1–42andcytochromecoxidasesubunit1 mayexplain,inpart,thediminishedenzymaticactivityofrespiratorychaincomplexIVandsubsequentneuronalmetabolic dysfunctionobservedinAD. Citation:Hernandez-ZimbronLF,Luna-Mun?ozJ,MenaR,Vazquez-RamirezR,Kubli-Gar