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Title: Regulation of gamma-Secretase in Alzheimer's Disease

Abstract

The {gamma}-secretase complex is an intramembrane aspartyl protease that cleaves its substrates along their transmembrane regions. Sequential proteolytic processing of amyloid precursor protein by {beta}- and {gamma}-secretase produces amyloid {beta}-peptides, which are the major components of amyloid plaques in the brains of Alzheimer's disease patients. The {gamma}-secretase complex is therefore believed to be critical in the pathogenesis of Alzheimer's disease. Here we review the range of factors found to affect the nature and degree of {gamma}-secretase complex activity; these include {gamma}-secretase complex assembly and activation, the integral regulatory subunit CD147, transient or weak binding partners, the levels of cholesterol and sphingolipids in cell membranes, and inflammatory cytokines. Integrated knowledge of the molecular mechanisms supporting the actions of these factors is expected to lead to a comprehensive understanding of the functional regulation of the {gamma}-secretase complex, and this, in turn, should facilitate the development of novel therapeutic strategies for the treatment of Alzheimer's disease.

Authors:
; ; ;
Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director, Office of Science; National Institutes ofHealth
OSTI Identifier:
918642
Report Number(s):
LBNL-62789
Journal ID: ISSN 0006-2960; BICHAW; R&D Project: L0454, L0205; TRN: US200819%%371
DOE Contract Number:
DE-AC02-05CH11231; NIH1R21GM070511,2R01GM054132
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 46; Journal Issue: 10; Related Information: Journal Publication Date: 03/13/2007
Country of Publication:
United States
Language:
English
Subject:
59; CELL MEMBRANES; CHOLESTEROL; DISEASES; FUNCTIONALS; LYMPHOKINES; PATHOGENESIS; PATIENTS; PRECURSOR; PROCESSING; PROTEINS; REGULATIONS; SUBSTRATES; TRANSIENTS

Citation Formats

Zhou, Shuxia, Zhou, Hua, Walian, Peter, and Jap, Bing. Regulation of gamma-Secretase in Alzheimer's Disease. United States: N. p., 2007. Web. doi:10.1021/bi602509c.
Zhou, Shuxia, Zhou, Hua, Walian, Peter, & Jap, Bing. Regulation of gamma-Secretase in Alzheimer's Disease. United States. doi:10.1021/bi602509c.
Zhou, Shuxia, Zhou, Hua, Walian, Peter, and Jap, Bing. Wed . "Regulation of gamma-Secretase in Alzheimer's Disease". United States. doi:10.1021/bi602509c.
@article{osti_918642,
title = {Regulation of gamma-Secretase in Alzheimer's Disease},
author = {Zhou, Shuxia and Zhou, Hua and Walian, Peter and Jap, Bing},
abstractNote = {The {gamma}-secretase complex is an intramembrane aspartyl protease that cleaves its substrates along their transmembrane regions. Sequential proteolytic processing of amyloid precursor protein by {beta}- and {gamma}-secretase produces amyloid {beta}-peptides, which are the major components of amyloid plaques in the brains of Alzheimer's disease patients. The {gamma}-secretase complex is therefore believed to be critical in the pathogenesis of Alzheimer's disease. Here we review the range of factors found to affect the nature and degree of {gamma}-secretase complex activity; these include {gamma}-secretase complex assembly and activation, the integral regulatory subunit CD147, transient or weak binding partners, the levels of cholesterol and sphingolipids in cell membranes, and inflammatory cytokines. Integrated knowledge of the molecular mechanisms supporting the actions of these factors is expected to lead to a comprehensive understanding of the functional regulation of the {gamma}-secretase complex, and this, in turn, should facilitate the development of novel therapeutic strategies for the treatment of Alzheimer's disease.},
doi = {10.1021/bi602509c},
journal = {Biochemistry},
number = 10,
volume = 46,
place = {United States},
year = {Wed Feb 07 00:00:00 EST 2007},
month = {Wed Feb 07 00:00:00 EST 2007}
}