γ-分泌酶基因与疾病表型的相关性研究

Correlation between γ-secretase gene and disease phenotype

γ-分泌酶复合体是一种大分子量膜整合蛋白酶复合体,包括早老素、单过性跨膜蛋白、前咽缺陷蛋白1和早老素增强子2四个亚基。γ-分泌酶能够切割多种I型跨膜蛋白,例如淀粉样蛋白前体蛋白、Notch受体、N-钙粘蛋白、E-钙粘蛋白和血管内皮生长因子受体1(VEGFR-1)。γ-分泌酶通过影响Notch信号通路,改变基因的转录和表达,参与多种疾病的发生,如化脓性汗腺炎、阿尔茨海默病、心肌疾病、肿瘤及痴呆。本文综述了γ-分泌酶基因的分类、定位、功能以及与疾病表型的相关性。

γ-secretase is a kind of macromolecular membrane-integrated protease complex,including four subunits presenilin（ PS）,Nicastrin,（ NCSTN）,anterior-pharynx-defective-1（ APH-1） and presenilin enhancer-2（ PEN-2）. It can be used to cleave a variety of type I transmembrane proteins,such as amyloid precursor protein（ APP）,Notch receptor,N-cadherin and vascular endothelial growth factor receptor 1（ VEGFR-1）. It has been found that γ-secretase affects the genes transcription and expression by affecting Notch signaling pathway and is involved in some diseases,such as suppurative sweat gland inflammation,Alzheimer＇s disease,cardiomyopathy,tumor and dementia. This paper summarizes the classification,localization,function and relevance of the γ-secretase gene.