《生命科学》 2009, 21(4): 508-512

治疗阿尔茨海默病的早老素/g-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：摘　要：阿尔茨海默病(Alzheimer抯 disease，AD) 又称老年痴呆症，是一种中枢神经系统(central nervous system， CNS)退行性疾病。b-淀粉样蛋白(b-amyloid，Ab42)被认为在阿尔茨海默病(AD)的发生、发展过程中起核心作用。Ab42由APP经b-和g-分泌酶相继切割产生。g-分泌酶是一个蛋白酶复合体，早老素(presenilin，PS) 是g-分泌酶的催化组分。因此，抑制PS/g分泌酶的活性是治疗AD的关键，因而PS/g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/g-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；g-分泌酶；抑制剂；调节剂

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: Abstract: Alzheimer{$39}s disease is a central nervous system (CNS) degenerative diseases. Amyloid b-peptide(Ab42) is strongly responsible for the occurrence and development of Alzheimer{$39}s disease(AD). Ab42 peptide is resulted from the sequential proteoiytic cleavages of amyloid precursor protein (APP) by b- and g-secretases. g-secretase is a protease complex， and presenilin (PS) is the catalytic component of g-secretase complex. Therefore， inhibition of PS or g-secretase activity is the most effective way to treat AD， accordingly， PS or g-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 g-secretase activity are becoming the focus of attention for the treatment of Alzheimer{$39}s disease in recent years.
Key words：Alzheimer{$39}s disease; presenilin; g-secretase; inhibitor; regulator