Amyloid β-peptide interactions with neuronal and glial cell plasma membrane: Binding sites and implications for Alzheimer's disease

Yann Verdier, Márta Zarándi, Botond Penke

Research output: Contribution to journalReview article

216 Citations (Scopus)

Abstract

The extracellular accumulation of amyloid-beta (Aβ) in neuritic plaques is one of the characteristic hallmarks of Alzheimer's disease (AD), a progressive dementing neurodegenerative disorder of the elderly. By virtue of its structure, Aβ is able to bind to a variety of biomolecules, including lipids, proteins and proteoglycans. The binding of the various forms of Aβ (soluble or fibrillar) to plasma membranes has been studied with regard to the direct toxicity of Aβ to neurons, and the activation of a local inflammation phase involving microglia. The binding of Aβ to membrane lipids facilitates Aβ fibrillation, which in turn disturbs the structure and function of the membranes, such as membrane fluidity or the formation of ion channels. A subset of membrane proteins binds Aβ. The serpin-enzyme complex receptor (SEC-R) and the insulin receptor can bind the monomeric form of Aβ. The α7nicotinic acetylcholine receptor (α7nAChR), integrins, RAGE (receptor for advanced glycosylation end-products) and FPRL1 (formyl peptide receptor-like 1) are able to bind the monomeric and fibrillar forms of Aβ. In addition, APP (amyloid precursor protein), the NMDA-R (N-methyl-D-aspartate receptor), the P75 neurotrophin receptor (P75NTR), the CLAC-P/collagen type XXV (collagen-like Alzheimer amyloid plaque component precursor/collagen XXV), the scavenger receptors A, BI (SR-A, SR-BI) and CD36, a complex involving CD36, α6β1-integrin and CD47 have been reported to bind the fibrillar form of Aβ. Heparan sulfate proteoglycans have also been described as cell-surface binding sites for Aβ. The various effects of Aβ binding to these membrane molecules are discussed.

Original languageEnglish
Pages (from-to)229-248
Number of pages20
JournalJournal of Peptide Science
Volume10
Issue number5
DOIs
Publication statusPublished - May 1 2004

Keywords

  • Alzheimer's disease
  • Amyloid-beta
  • Membrane lipids
  • membrane proteins

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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