Binding sites of amyloid β-peptide in cell plasma membrane and implications for Alzheimer's disease

Yann Verdier, Botond Penke

Research output: Contribution to journalReview article

93 Citations (Scopus)

Abstract

The binding of amyloid beta peptides (Aβ) to plasma membranes appears to be a promising point of intervention in the events leading to the development of Alzheimer's disease (AD). This binding has been studied as regards the direct toxicity of Aβ on neurons, and the activation of a local inflammation phase involving microglia. By virtue of its structure, Aβ is able to bind to a variety of biomolecules, including lipids, proteoglycans and proteins. This review focuses on the membrane proteins that can mediate the interaction between Aβ and the plasma membranes in AD. On neurons, these are APP (amyloid precursor protein), the NMDA-R (N-methyl-D-aspartate receptor), integrins, the α7nicotinic acetylcholine receptor (α7nAChR), the P75 neurotrophin receptor (P75NTR) and the CLAC-P/collagen type XXV (collagen-like Alzheimer amyloid plaque component precursor/collagen XXV). On glial cells, FPRL1 (formyl peptide receptor-like 1), the scavenger receptors A, BI (SR-A, SR-BI) and CD36, a complex involving CD36, α6β1-integrin and CD47, and heparan sulfate proteoglycans have been reported to bind Aβ. It should be noted that integrins, RAGE (receptor for advanced glycosylation end-products), the Serpin-enzyme complex receptor (SEC-R) and the insulin receptor can bind Aβ and are present on neurons and on glial cells. After a presentation of the structure and the function of each of these proteins, the method used to prove their binding to Aβ is described, and the implication of this binding in AD is discussed. Finally, it is underlined that multireceptor complexes containing integrins may be involved in this interaction.

Original languageEnglish
Pages (from-to)19-31
Number of pages13
JournalCurrent Protein and Peptide Science
Volume5
Issue number1
DOIs
Publication statusPublished - Feb 1 2004

Keywords

  • APP
  • Alzheimer's disease
  • Amyloid-beta
  • Integrins
  • Membrane proteins
  • NMDA receptor
  • Scavenger receptors
  • α7nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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