摘要
阿尔茨海默病(Alzheimer's disease,AD)是老年人最常见的神经系统退行性疾病。经β-和γ-分泌酶切割形成的β淀粉样蛋白(amyloid-beta,Aβ)与AD的发生密切相关。γ-分泌酶是一个含有早老素的复合蛋白体,作为Aβ代谢的关键酶,它是治疗AD的潜力的靶点。在过去20年里,药物研究且发现了能抑制或调节γ-分泌酶的小分子化合物,部分化合物已经进入临床研究。本文就Aβ的形成、γ-分泌酶的结构及目前γ-分泌酶的抑制剂、调节剂的研究进展作一综述介绍。
Alzheimer＇s disease （AD） is the most common neurodegenerative disorder in the elderly. The amyloid-beta（Abeta） is strongly im- plicated the pathogenesis of AD, and it is cut out of the amyloid precursor protein （APP） by beta- and gamma-secretases. Gamma-seceretase, a complex of proteins containing presenilin and a key enzyme involved in Abeta generation, is a potential target in the development of drugs for AD therapy. During the past two decades, drug research has discovered small-molecule compounds that inhibit or modulate activity of this enzyme and some of these have already entered clinical trials. This review focuses on the studies of the formation of Abeta and the structure of gamma-seceretase, gamma-secretase inhibitors ,gamma-secretase modulators.
出处
《世界科技研究与发展》
CSCD
2012年第5期817-820,共4页
World Sci-Tech R&D
