治疗阿尔茨海默病的早老素γ-分泌酶抑制剂和调节剂.PDF

第21卷 第4期 生命科学 Vol. 21, No. 4 2009年8月 Chinese Bulletin of Life Sciences Aug., 2009 文章编号 ：1004-0374(2009)04-0508-05 治疗阿尔茨海默病的早老素/γ-分泌酶抑制剂和调节剂 陈天睿，黄雪媚，崔理立，张应玖* (吉林大学分子酶学工程教育部重点实验室，长春 130021) 摘　要：阿尔茨海默病(Alzheimer’s disease，AD) 又称老年痴呆症，是一种中枢神经系统(central ner- vous system, CNS)退行性疾病。β-淀粉样蛋白(β-amyloid，Aβ42)被认为在阿尔茨海默病(AD)的发生、 发展过程中起核心作用。Aβ42 由APP 经 β- 和 γ- 分泌酶相继切割产生。γ- 分泌酶是一个蛋白酶复合体， 早老素(presenilin，PS) 是γ- 分泌酶的催化组分。因此，抑制PS/γ分泌酶的活性是治疗AD 的关键， 因而PS/γ 分泌酶也是治疗AD 的主要靶点。根据这些理论，人们提出了一些治疗AD 的新方法，其中 PS/γ- 分泌酶抑制剂和调节剂成为近年来人们关注的焦点。 关键词：阿尔茨海默病；早老素；γ- 分泌酶；抑制剂；调节剂 中图分类号：R741.05，R592　　文献标识码：A Inhibitor and regulator of presenilin for Alzheimer’s disease 　 CHEN Tian-rui, HUANG Xue-mei, CUI Li-li, ZHANG Ying-jiu* (Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130021, China) Abstract: Alzheimer’s disease is a central nervous system (CNS) degenerative diseases. Amyloid β-peptide (Aβ42) is strongly responsible for the occurrence and development of Alzheimer’s disease(AD). Aβ42 peptide is resulted from the sequential proteoiytic cleavages of amyloid precursor protein (APP) by β- and γ-secretases. γ-secretase is a protease complex, and presenilin (PS) is the catalytic component of γ-secretase complex. Therefore, inhibition of PS or γ-secretase activity is the most effective way to treat AD, accordingly, PS or γ-secretase became a major target for AD treatment. Based on these thoughts, some methods of treating AD are put forward, and the inhibitors and regulators of PS or γ-