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Membrane rafts in Alzheimer's disease beta-amyloid production

Authors
Journal
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
1388-1981
Publisher
Elsevier
Publication Date
Volume
1801
Issue
8
Identifiers
DOI: 10.1016/j.bbalip.2010.03.007
Keywords
  • Alzheimer'S Disease
  • Amyloid
  • Amyloid Precursor Protein
  • Cholesterol
  • Palmitoylation
  • Lipid Rafts
Disciplines
  • Biology
  • Medicine

Abstract

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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