α-、β-和γ-分泌酶对淀粉样前体蛋白（APP）切割的调控

Regulation of APP cleavage by alpha-, beta- and gamma-secretases.

作者信息

Nunan J, Small D H

机构信息

Laboratory of Molecular Neurobiology, Department of Pathology, University of Melbourne, 3010, Melbourne, Vic., Australia.

出版信息

FEBS Lett. 2000 Oct 13;483(1):6-10. doi: 10.1016/s0014-5793(00)02076-7.

DOI:10.1016/s0014-5793(00)02076-7

PMID:11033346

Abstract

Proteolytic cleavage of the amyloid protein from the amyloid protein precursor (APP) by APP secretases is a key event in Alzheimer's disease (AD) pathogenesis. alpha-Secretases cleave APP within the amyloid sequences, whereas beta- and gamma-secretases cleave on the N- and C-terminal ends respectively. The transmembrane aspartyl protease BACE has been identified as beta-secretase and several proteases (ADAM-10, TACE, PC7) may be alpha-secretases. A number of studies have suggested that presenilins could be gamma-secretases, although this remains to be demonstrated conclusively. Inhibition of beta- and gamma-secretase, or stimulation of alpha-secretase, is a rational strategy for therapeutic intervention in AD.

摘要

淀粉样前体蛋白（APP）经APP分泌酶进行蛋白水解切割是阿尔茨海默病（AD）发病机制中的关键事件。α-分泌酶在淀粉样序列内切割APP，而β-分泌酶和γ-分泌酶分别在N端和C端进行切割。跨膜天冬氨酰蛋白酶BACE已被确定为β-分泌酶，几种蛋白酶（ADAM-10、TACE、PC7）可能是α-分泌酶。许多研究表明早老素可能是γ-分泌酶，尽管这一点仍有待最终证实。抑制β-和γ-分泌酶，或刺激α-分泌酶，是对AD进行治疗干预的合理策略。