Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease.
The extracellular accumulation of amyloid-beta (Abeta) 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, Abeta is able to bind to a variety of biomolecules, including lipids, proteins and proteoglycans. The binding of the various forms of Abeta (soluble or fibrillar) to plasma membranes has been studied with regard to the direct toxicity of Abeta to neurons, and the activation of a local inflammation phase involving microglia. The binding of Abeta to membrane lipids facilitates Abeta 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 Abeta. The serpin-enzyme complex receptor (SEC-R) and the insulin receptor can bind the monomeric form of Abeta. The alpha7nicotinic acetylcholine receptor (alpha7nAChR), 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 Abeta. 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, alpha6beta1-integrin and CD47 have been reported to bind the fibrillar form of Abeta. Heparan sulfate proteoglycans have also been described as cell-surface binding sites for Abeta. The various effects of Abeta binding to these membrane molecules are discussed.
Verdier
Yann
Y
Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
Zarándi
Márta
M
Penke
Botond
B
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D015703:Antigens, CD / Q000378:metabolism; D051928:CD47 Antigen; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D050356:Lipid Metabolism; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D007473:Ion Channels; D011509:Proteoglycans; D011956:Receptors, Cell Surface