SUBSTRATES FOR METALLOENDOPEPTIDASES IN THE CENTRAL NERVOUS SYSTEM
SUBSTRATES FOR METALLOENDOPEPTIDASES IN THE CENTRAL NERVOUS SYSTEM
复制标题
DOI：
10.1142/9781860947179_0004
复制
发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Zimmermann, D. R.
中科院分区：
文献类型：
--
作者：
Gottschall, P. E.;Sandy, J. D.;Zimmermann, D. R.
基质金属蛋白酶(MMPs)和相关的基质降解金属内肽酶(ADAMTS和ADAMS)最常出现在与细胞和组织重塑有关的生理和病理事件中，并顾名思义，在细胞外基质(ECM)蛋白和非基质蛋白底物的切割和/或降解中发挥作用。其他来源，包括本书中的章节，描述了MMPs是神经系统关键功能的重要调节器，从发育过程中的祖细胞迁移到神经胶质细胞的分化，再到促进轴突萌发(1，2)。然而，金属内肽酶在发育生理学中的关键作用在某种程度上掩盖了它们在成人从多发性硬化症到脑血管中风到阿尔茨海默病等各种神经病理中的组织破坏潜力。然而，在这方面，应该指出的是，即使在成人神经系统中，金属内肽酶的作用显然也不限于病理效应。然而，主要作用于细胞外的蛋白水解酶，通常是通过结合和切割基质底物来影响细胞行为的？尽管金属内肽酶可以通过“受体”直接激活细胞内的信号通路，但它们的
The matrix metalloproteinases (MMPs) and related matrix-degrading metalloendopeptidases (ADAMTSs and ADAMs) most often appear in physiology and pathology during events related to cell and tissue remodelling, and function per their name, in the cleavage and/or degradation of extracellular matrix (ECM) proteins as well as non-matrix protein substrates. Other sources including chapters in this volume have delineated the fact that MMPs are important modulators of key functions in the nervous system from progenitor migration during development, to differentiation of glial cells, to enhancing axonal sprouting (1, 2). Yet the crucial role for metalloendopeptidases in developmental physiology somewhat belies their potential for tissue destruction in various neuropathologies in the adult ranging from multiple sclerosis to cerebrovascular stroke to Alzheimer’s disease. In this regard, however, it should be noted that even in the adult nervous system, the actions of metalloendopeptidases are clearly not confined to pathological effects. Yet, how do proteolytic enzymes that primarily act outside cells, most often by binding to and cleaving matrix substrates, influence cell behaviour? Although metalloendopeptidases may directly activate intracellular signalling pathways via ‘receptors’, their