Dubois B, Opdenakker G, Carton H
Rega Institute for Medical Research, Leuven, Belgium.
Acta Neurol Belg. 1999 Mar;99(1):53-6.
The matrix metalloproteases (MMPs) are a family of structurally related proteolytic enzymes, that are involved in various physiological and pathological processes. In the central nervous system, MMPs may contribute to proteolysis of basement membranes, extracellular matrix molecules, cytokine precursors, zymogens, cell surface molecules, and myelin components. Clipping of the latter increases the local antigenic epitope load. We explain the REGA model (Remnant Epitopes Generate Autoimmunity), which may be applied to the pathophysiology of many autoimmune diseases, including multiple sclerosis, and which consists of a tight control of the enzymatic activity of the MMPs at several levels: MMP gene transcription and MMP secretion, that are regulated by cytokines and chemokines, activation of latent zymogens by proteolysis, inhibition of enzyme activity by specific inhibitors, and glycosylation. Gelatinase B, a rather complex protease, is discussed as a prototypic MMP example. Possible applications of our understanding about the regulation of MMP activity and of the influence on disease-promotion or -limitation are reviewed.
基质金属蛋白酶（MMPs）是一类结构相关的蛋白水解酶家族，参与多种生理和病理过程。在中枢神经系统中，MMPs可能有助于基底膜、细胞外基质分子、细胞因子前体、酶原、细胞表面分子和髓鞘成分的蛋白水解。后者的剪切增加了局部抗原表位负荷。我们解释了REGA模型（残余表位引发自身免疫），该模型可应用于包括多发性硬化症在内的许多自身免疫性疾病的病理生理学，它包括在多个水平对MMPs酶活性的严格控制：MMP基因转录和MMP分泌，它们受细胞因子和趋化因子调节；通过蛋白水解激活潜伏酶原；通过特异性抑制剂抑制酶活性；以及糖基化。明胶酶B是一种相当复杂的蛋白酶，作为MMP的典型例子进行了讨论。综述了我们对MMP活性调节及其对疾病促进或限制影响的理解的可能应用。
