Membrane rafts in Alzheimer's disease beta-amyloid production |
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Authors: | Kulandaivelu S Vetrivel Gopal Thinakaran |
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Institution: | Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USA |
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Abstract: | Alzheimer's disease (AD), the most common age-associated dementing disorder, is pathologically manifested by progressive cognitive dysfunction concomitant with the accumulation of senile plaques consisting of amyloid-β (Aβ) peptide aggregates in the brain of affected individuals. Aβ is derived from a type I transmembrane protein, amyloid precursor protein (APP), by the sequential proteolytic events mediated by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. Multiple lines of evidence have implicated cholesterol and cholesterol-rich membrane microdomains, termed lipid rafts in the amyloidogenic processing of APP. In this review, we summarize the cell biology of APP, β- and γ-secretases and the data on their association with lipid rafts. Then, we will discuss potential raft targeting signals identified in the secretases and their importance on amyloidogenic processing of APP. |
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Keywords: | APP amyloid precursor protein PS presenilin (s) BACE1 β-site APP cleaving enzyme 1 Aβ β-amyloid CTF C-terminal fragment TGN trans-Golgi network DIM detergent-insoluble membrane VAMP Vesicle-associated membrane protein |
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