Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
J Neurochem. 2011 Jan;116(1):22-32. doi: 10.1111/j.1471-4159.2010.07082.x. Epub 2010 Dec 2.
Matrix metalloproteinase-3 (MMP-3) is a member of the class of zinc-dependent proteases known to degrade the extracellular matrix. MMP-3 activity is regulated at three different levels: gene expression, proteolytic activation of the zymogen, and inhibition by the endogenous tissue inhibitors of metalloproteinase. A line of evidence indicates a role of MMP-3 in neurodegeneration. In neuronal cells, MMP-3 expression is increased in response to cell stress, and the cleaved, active MMP-3 participates in apoptotic signaling. In the extracellular space, MMP-3 triggers microglia to produce proinflammatory and cytotoxic molecules as well as MMP-3, which in turn contribute to neuronal damage. MMP-3 is increased in various experimental models of Parkinson's disease that are produced by selective toxins and by inflammagen, and the neuronal death is attenuated by various ways that inhibit MMP-3. α-Synuclein, whose gene mutations are associated with familial forms of Parkinson's disease, is proteolyzed by MMP-3. Contribution of MMP-3 toward the pathogenesis of Alzheimer's disease and other neurodegenerative diseases has also been suggested. Thus, modulation of MMP-3 expression and/or activity could be of therapeutic value for neurodegenerative diseases.
基质金属蛋白酶-3（MMP-3）是锌依赖性蛋白酶家族的成员，已知其可降解细胞外基质。MMP-3 的活性在三个不同水平上受到调节：基因表达、酶原的蛋白水解激活以及内源性金属蛋白酶组织抑制剂的抑制。有一系列证据表明 MMP-3 在神经退行性变中起作用。在神经元细胞中，MMP-3 的表达在细胞应激时增加，而裂解的、活性的 MMP-3 参与细胞凋亡信号转导。在细胞外空间，MMP-3 触发小胶质细胞产生促炎和细胞毒性分子以及 MMP-3，这反过来又导致神经元损伤。在通过选择性毒素和致炎剂产生的各种帕金森病实验模型中，MMP-3 增加，并且通过各种抑制 MMP-3 的方式减轻神经元死亡。与家族性帕金森病相关的基因突变的α-突触核蛋白被 MMP-3 蛋白水解。MMP-3 对阿尔茨海默病和其他神经退行性疾病发病机制的贡献也已被提出。因此，调节 MMP-3 的表达和/或活性可能对神经退行性疾病具有治疗价值。
