Center for Human Genetics, KULeuven, Leuven, Belgium.
Curr Top Dev Biol. 2010;92:201-30. doi: 10.1016/S0070-2153(10)92006-1.
Gamma-secretase is the crucial proteolytic activity that releases the Notch intracellular domain and is therefore a central player in the canonical Notch-signaling transduction pathway. We discuss here briefly the discovery of gamma-secretase and what is known on its structure and function. Recent work also indicates that the assembly and activity of gamma-secretase might be regulated by novel cell biological mechanisms. Finally we explore the recent insight that there are several gamma-secretase complexes in mammalian and discuss possibilities to use gamma-secretase as a drug target in Alzheimer's disease and cancer.
γ-分泌酶是一种关键的蛋白水解酶，可释放 Notch 细胞内结构域，因此是经典 Notch 信号转导通路的核心组成部分。在这里，我们简要讨论了 γ-分泌酶的发现，以及其结构和功能的现有认识。最近的研究工作还表明，γ-分泌酶的组装和活性可能受到新的细胞生物学机制的调节。最后，我们探讨了哺乳动物中存在几种 γ-分泌酶复合物的最新研究进展，并讨论了将 γ-分泌酶作为阿尔茨海默病和癌症药物靶点的可能性。
