Sci. Aging Knowl. Environ., 10 October 2001
Vol. 2001, Issue 2, p. or8


A Portrait of Alzheimer Secretases

William P. Esler, and Michael S. Wolfe;2001/2/or8

Abstract: Science 293, 1449-1454 (2001).

The amyloid {beta}-peptide (A) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40- to 42-amino acid peptide is formed by the cleavage of the A{beta} precursor protein (APP). The three proteases that cleave APP, {alpha}-, {beta}-, and {gamma}-secretases, have been implicated in the etiology of AD. {beta}-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and {alpha}-secretase displays characteristics of certain membrane-tethered metalloproteases. {gamma}-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the {alpha}-, {beta} -, and {gamma}-secretases provides potential targets for designing new drugs to treat AD.

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