An empirical model of gamma-secretase activity.
An empirical model of gamma-secretase activity.
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γ-分泌酶活性的经验模型。
DOI：
10.1111/j.1749-6632.2000.tb06928.x
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发表时间：
2000
影响因子：
5.2
通讯作者：
Golde,TE
中科院分区：
文献类型：
--
作者：
Murphy,MP;Wang,R;Fraser,PE;Fauq,A;Golde,TE
摘要：γ - Secretase催化a β羧基末端的裂解，将其从APP中释放出来。虽然γ - Secretase是治疗阿尔茨海默病（AD）的主要治疗药物靶点，但它似乎是一种不寻常的蛋白水解活性，迄今为止，尚未发现负责该活性的蛋白酶。基于APP跨膜结构域（TMD）突变体的研究，很明显，存在多种药理学上不同的γ -分泌酶活性，这些活性受到空间限制，而早老素（PS）以蛋白酶独立的方式调节γ -分泌酶的裂解。基于这些研究，我们提出了γ -分泌酶活性的多蛋白酶模型，并预测γ -分泌酶可能是密切相关的蛋白酶。
Abstract:γ‐Secretase catalyzes the cleavage at the carboxyl terminus of Aβ to release it from the APP. While γ‐secretase is a major therapeutic drug target for the treatment of Alzheimer's disease (AD), it appears to be an unusual proteolytic activity, and, to date, no protease responsible for this activity has been identified. Based on studies of APP transmembrane domain (TMD) mutants, it is apparent that there are multiple pharmacologically distinct γ‐secretase activities that are spatially restricted and that presenilins (PS) regulate cleavage by γ‐secretases in a protease independent fashion. Based on these studies, we propose a multiprotease model for γ‐secretase activity and predict that the γ‐secretases are likely to be closely related proteases.