γ分泌酶研究新进展:γ分泌酶激活蛋白

β淀粉样蛋白(Aβ)聚集是阿尔茨海默病(AD)的重要病理特征之一,γ分泌酶对Aβ形成起关键作用,但γ分泌酶存在多种底物蛋白,目前多种在研究的γ分泌酶抑制剂临床试验均因同时抑制其他底物蛋白而产生严重不良反应被终止。γ分泌酶激活蛋白(GSAP)可激活γ分泌酶特异性裂解产生Aβ,因此通过抑制GSAP,可选择性减少Aβ,而不影响其他蛋白裂解,有望成为AD的治疗靶点。文中就γ分泌酶激活蛋白生物特性、作用机制及调控因子等进行综述。

Recent Advances of γ-secretase：γ-secretase Activating Protein

ABSTRACTAmyloid β-protein (Aβ) peptides aggregation is one of the main pathological characteristics of Alzheimer`s disease (AD). γ-secretase plays a key role of the formation of Aβ, and can react with many kinds of substrate proteins. So many clinical trials of γ-secretase inhibitors were ceased for severe adverse effects, which resulted from blocking many other substrates of γ-secretase. γ-secretase activating protein (GSAP), which can selectively activate γ-secretase to produce Aβ, was introduced. It has been reported that inhibiting GSAP could reduce Aβ without impairing other substrates, which makes GSAP a potential therapeutic target for AD.