期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1502, 期 1, 页码 145-157出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0925-4439(00)00041-7
关键词
receptor; amyloid beta-peptide; alcohol dehydrogenase reductase; cell stress; apoptosis; cytotoxicity
资金
- NIA NIH HHS [AG00690, AG14103, AG16736] Funding Source: Medline
Insights into factors underlying causes of familial Alzheimer's disease (AD), such as mutant forms of beta-amyloid precursor protein and presenilins, and those conferring increased risk of sporadic AD, such as isoforms of apolipoprotein E and polymorphisms of alpha(2)-macroglobulin, have been rapidly emerging. However, mechanisms through which amyloid beta-peptide (A beta), the fibrillogenic peptide most closely associated with neurotoxicity in AD, exerts its effects on cellular targets have only been more generally outlined. Late in the course of AD, when A beta fibrils are abundant, non-specific interactions of amyloid with cellular elements are likely to induce broad cytotoxicity. However, early in AD, when concentrations of A beta are much lower and extracellular deposits are infrequent, mechanisms underlying cellular dysfunction have not been clearly defined. The key issue in elucidating the means through which A beta perturbs cellular properties early in AD is the possibility that protective therapy at such times may prevent cytotoxicity at a point when damage is still reversible. This brief review focusses on two cellular cofactors for A beta-induced cellular perturbation: the cell surface immunoglobulin superfamily molecule RAGE (receptor for advanced glycation endproducts) and ABAD (A beta binding alcohol dehydrogenase). Although final proof for the involvement of these cofactors in cellular dysfunction in AD must await the results of further in vivo experiments, their increased expression in AD brain, as well as other evidence described below, suggests the possibility of specific pathways for A beta-induced cellular perturbation which could provide future therapeutic targets. (C) 2000 Elsevier Science B.V. All rights reserved.
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