治疗阿尔茨海默病的早老素/γ-分泌酶抑制剂和调节剂

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 nervous 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。

Inhibitor and regulator of presenilin for Alzheimer＇s disease

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-secretase activity are becoming the focus of attention for the treatment of Alzheimer＇s disease in recent years.