γ-secretase as a therapeutic target for treatment of Alzheimer's disease

被引：32

作者：

Tomita, T ^{[1
]}

Iwatsubo, T ^{[1
]}

机构：

[1] Univ Tokyo, Dept Neuropathol & Neurosci, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

来源：

CURRENT PHARMACEUTICAL DESIGN | 2006年 / 12卷 / 06期

关键词：

Alzheimer's disease; A beta; amyloid; gamma-secretase; presenilin; aspartic protease; intramembrane proteolysis; protease inhibitor;

D O I：

10.2174/138161206775474206

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Alzheimer's disease (AD) is the most common cause of dementia with aging, that is pathologically characterized by senile plaques that contain amyloid-P peptides (A beta) and neurofibrillary tangles comprised of phosphorylated tau. Genetic and biological studies provide evidence that the production and deposition of A beta contribute to the etiology of AD. gamma-Secretase is the pivotal enzyme in generating the C terminus of A beta, that determines its aggregability and propensity for deposition. Drugs that regulate the production of A beta by inhibiting gamma-secretase activity could provide an effective therapeutics for AD, although recent studies suggest that gamma-secretase plays important roles in novel signaling pathways that play essential roles in embryonic development. This review focuses on recent progresses in the gamma-sccretase biology that shed substantial light on the proteolytic, mechanism, regulation and composition of this unusual enzyme. Moreover, we review the recent development of inhibitors and provide a direction for the effective treatment of AD through inhibition of gamma-secretase activity.

引用

页码：661 / 670

页数：10

共 136 条

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