Department of Clinical and Biological Sciences, Faculty of Medicine San Luigi Gonzaga, University of Turin, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
Curr Pharm Des. 2014;20(18):2993-3018. doi: 10.2174/13816128113196660701.
Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS). This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.
细胞外基质的降解是胚胎发育、形态发生、血管生成、组织修复和重塑的一个重要特征。它在生理条件下受到精确调节，但当失调时，它会成为许多疾病的原因，包括动脉粥样硬化、骨关节炎、糖尿病血管并发症和神经退行性变。各种类型的蛋白酶都与细胞外基质的降解有关，但主要的酶被认为是金属蛋白酶，如基质金属蛋白酶（MMPs）和解整合素金属蛋白酶域（ADAMs），其中包括含有血栓素结构域的 ADAMs（ADAMTS）。这篇综述讨论了主要金属蛋白酶在一些与年龄相关的慢性疾病中的作用，并研究了目前对其抑制剂的有益作用的了解，这些抑制剂被用作治疗或预防这些疾病的发展和进展的新治疗策略。
