title: Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease.
abstract: Alzheimer disease (AD) is the most prevalent cause of dementia. Amyloid-β (Aβ) oligomers are potent synaptotoxins thought to mediate AD-related phenotypes. Cellular prion protein (PrP(C)) has been identified as a high-affinity receptor for Aβ oligomers. Herein, we review the functional consequences of Aβ oligomer binding to PrP(C) on the neuronal surface. We highlight recent evidence that Fyn kinase mediates signal transduction downstream of the PrP(C)-Aβ oligomer complex. These studies suggest that PrP(C) has a central role in AD pathogenesis and may provide a target for therapeutic intervention in AD.
authors.affiliation: Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Um
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D017774:Long-Term Potentiation; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018621:PrPC Proteins / Q000032:analysis / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D018621:PrPC Proteins; D051076:Proto-Oncogene Proteins c-fyn