摘要
γ分泌酶是膜整合蛋白酶复合体,可以切割多种I型跨膜蛋白,近年来由于它与阿尔茨海默病发病密切相关而受到广泛关注。γ分泌酶介导的膜内切割是一个非常复杂的过程,这和它复杂的内部结构和作用机制有关。最新的研究表明γ分泌酶PS亚基的活性位点附近有一个GXGD结构域,它对于γ分泌酶的催化活性有重要作用;"含水腔隙"的发现使γ分泌酶在高度疏水的脂质双分子层内的底物切割成为可能。该文综述了近年来γ分泌酶结构和功能的研究进展,阐述了γ分泌酶切割淀粉样蛋白前体APP释放淀粉样蛋白Aβ的过程,并且指出了γ分泌酶结构功能的研究进展对阿尔茨海默病治疗的重要意义。
γ-secretase is a multiprotein complex responsible for the intramembrane cleavage of type I transmem-brane proteins. Research on Alzheimer＇s disease pathogenesis lead to the identification of γ-secretase,because it mediates the final proteolytic cleavage,which liberates amyloid β-peptide（Aβ） ,the major component of senile plaques in the brain of Alzheimer＇s disease patients. It was recently found that a GXGD motif around the active sites of PS is important for the γ-secretase-cleavage and the water-containing-cavity made the intramembrane cleavage in the highly hydrophobic environment possible. This article reviews the latest research progresses on the structure and function of γ-secretase and the cleavage of APP,which releases Aβ. γ-secretase is the potential drug target for Alzheimer＇s disease.
出处
《生命科学》
CSCD
北大核心
2010年第9期913-918,共6页
Chinese Bulletin of Life Sciences
