期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 20, 期 2, 页码 219-224出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2008.12.011
关键词
Protease; Amyloid; Notch receptor; Inhibitors; Therapeutics
资金
- NIH [R01 AG17574, R01 NS41355, P01 AG15379]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041355] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG015379, R01AG017574] Funding Source: NIH RePORTER
gamma-Secretase is a membrane-embedded proteolytic complex composed of presenilin and three other subunits. The gamma-secretase complex generates the amyloid beta-peptide of Alzheimer's disease but also plays important roles in normal physiology, especially in signaling from the Notch receptor. How this hydrolytic enzyme works in a hydrophobic environment is largely unanswered, but mutagenesis and chemical probes have offered insight. gamma-Secretase is an important therapeutic target, although mechanism-based toxicity presents a serious obstacle. Agents that lower amyloid beta-peptide production while leaving important normal functions of gamma-secretase intact are promising therapeutic leads. Inhibition of Notch signaling by gamma-secretase inhibitors, which is undesirable for the prevention or treatment of Alzheimer's disease, may be beneficial for the treatment of a variety of cancers. (C) 2009 Elsevier Ltd. All rights reserved.
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