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膜内天冬氨酸蛋白酶2,一种阿尔茨海默病的药物靶点。

Memapsin 2, a drug target for Alzheimer's disease.

作者信息

Koelsch Gerald, Turner Robert T, Hong Lin, Ghosh Arun K, Tang Jordan

机构信息

Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma Medical Center, Oklahoma City, OK 73104, USA.

出版信息

Biochem Soc Symp. 2003(70):213-20. doi: 10.1042/bss0700213.

Abstract

Mempasin 2, a beta-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of beta-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of beta-amyloid.

摘要

膜天冬氨酸蛋白酶2是一种β-分泌酶,是一种膜锚定天冬氨酸蛋白酶,它启动淀粉样前体蛋白的切割,导致β-淀粉样蛋白的产生和阿尔茨海默病的发病。因此,膜天冬氨酸蛋白酶2是开发该疾病抑制剂药物的主要治疗靶点。已经建立了许多生化工具,如特异性和晶体结构,并由此设计出了强效且相对较小的过渡态抑制剂。尽管开发一种临床上可行的膜天冬氨酸蛋白酶2抑制剂仍然具有挑战性,但迄今为止取得的进展让人看到希望,即膜天冬氨酸蛋白酶2抑制剂最终可能有助于治疗性降低β-淀粉样蛋白水平。

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