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.
Keywords:
Alzheimer disease; Fyn kinase; PrpC; cellular prion protein; prion.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / analysis
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Amyloid beta-Peptides / metabolism*
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Animals
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Brain / metabolism
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Brain / pathology
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Brain / physiopathology
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Humans
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Long-Term Potentiation
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Memory Disorders / metabolism
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Memory Disorders / pathology
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Memory Disorders / physiopathology
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Neurons / metabolism
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Neurons / pathology*
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PrPC Proteins / analysis
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PrPC Proteins / metabolism*
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Proto-Oncogene Proteins c-fyn / metabolism*
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Signal Transduction
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Synapses / metabolism
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Synapses / pathology
Substances
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Amyloid beta-Peptides
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PrPC Proteins
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Proto-Oncogene Proteins c-fyn