γ-分泌酶的空间结构及调节剂的研究进展

发布时间：2018-01-23 10:54

本文关键词： γ-分泌酶阿尔茨海默病蛋白质结构三级信号传导 γ-分泌酶调节剂　出处：《中国药理学与毒理学杂志》2015年06期 　论文类型：期刊论文

【摘要】：γ-分泌酶是与阿尔茨海默病相关的Ⅰ型跨膜蛋白酶。它包括早老素、早老素增强子2、前咽缺陷蛋白1和呆蛋白(nicastrin)4个亚基。最近研究利用超低温电子显微镜在高分辨率的条件下首次揭示了人源γ-分泌酶"马蹄形"的三维空间结构以及各亚基的排列顺序,有助于更深入地认识该酶的调控通路及作用机制。此外,包括非甾体类抗炎药等在内的γ-分泌酶调节剂在体外实验中被证实能抑制γ-分泌酶的活性并选择性地降低β淀粉样蛋白片段42的水平,为阿尔茨海默病的防治提供了有效途径,具有广阔的开发前景,成为近年来的研究热点。本文就γ-分泌酶各亚基调控通路、人源γ-分泌酶的精细三维空间结构以及γ-分泌酶的调节剂进行综述。
[Abstract]:纬 -secretase is a type I transmembrane protease associated with Alzheimer's disease. Propharyngeal defect protein 1 and daemon protein nicastrin). Four subunits. Recently, the three-dimensional spatial structure of human 纬 -secretase "horseshoe" and the arrangement order of each subunit were first revealed by using ultra-low temperature electron microscope under the condition of high resolution. It is helpful to further understand the regulation pathway and mechanism of the enzyme. 纬 -secretory enzyme modulators, including non-steroidal anti-inflammatory drugs, have been shown to inhibit the activity of 纬 -secretase and selectively reduce the level of 尾 -amyloid protein fragment 42 in vitro. It provides an effective way for the prevention and treatment of Alzheimer's disease and has a broad prospect of development. It has become a hot research topic in recent years. This article focuses on the regulation pathway of 纬 -secretase subunits. The fine three-dimensional structure of human 纬-secretase and the regulator of 纬-secretase were reviewed.
【作者单位】：三峡大学医学院国家中药药理科研三级实验室;
【基金】：湖北省自然科学基金项目(2013CFC066) 宜昌市科学研究与开发项目(A13301-57) 三峡大学研究生科研创新基金项目~~
【分类号】：R749.16
【正文快照】： 阿尔茨海默病(Alzheime disease,AD)又称老年性痴呆症,是一种常见的与年龄密切相关的神经退行性疾病[1]。越来越多的研究证明,长时程AD病理进程还会引发患者整体慢性系统性病变,如造成脑组织功能代谢障碍、引起外周血液一些生理生化指标异常、缓慢干扰机体各组织器官自稳态[2]

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