The metalloproteinase (MP) family of zinc-dependent proteases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteases (ADAMs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) plays a crucial role in the extracellular matrix (ECM) remodeling and degradation activities. A wide range of substrates of the MP family includes ECM components, chemokines, cell receptors, and growth factors. Metalloproteinases activities are tightly regulated by proteolytic activation and inhibition via their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the imbalance of the activation and inhibition is responsible in progression or inhibition of several diseases, e.g., cancer, neurological disorders, and cardiovascular diseases. We provide an overview of the structure, function, and the multifaceted role of MMPs, ADAMs, and TIMPs in several diseases via their cellular functions such as proteolysis of other cell signaling factors, degradation and remodeling of the ECM, and other essential protease-independent interactions in the ECM. The significance of MP inhibitors targeting specific MMP or ADAMs with high selectivity is also discussed. Recent advances and techniques used in developing novel MP inhibitors and MP responsive drug delivery tools are also reviewed.

中文翻译：

---

金属蛋白酶及其抑制剂：开发新疗法的潜力。


锌依赖性蛋白酶的金属蛋白酶 (MP) 家族，包括基质金属蛋白酶 (MMP)、解整合素和金属蛋白酶 (ADAM) 以及具有血小板反应蛋白基序的解整合素和金属蛋白酶 (ADAMTS)，在细胞外基质 (ECM) 重塑中发挥着至关重要的作用和降解活动。 MP 家族的多种底物包括 ECM 成分、趋化因子、细胞受体和生长因子。金属蛋白酶的活性通过其天然抑制剂、金属蛋白酶组织抑制剂 (TIMP) 受到蛋白水解激活和抑制的严格调节，激活和抑制的不平衡导致多种疾病的进展或抑制，例如癌症、神经系统疾病和心血管疾病疾病。我们通过 MMP、ADAM 和 TIMP 的细胞功能（例如其他细胞信号传导因子的蛋白水解、ECM 的降解和重塑以及其他重要的不依赖蛋白酶的细胞功能），概述了 MMP、ADAM 和 TIMP 的结构、功能和在多种疾病中的多方面作用。 ECM 中的相互作用。还讨论了高选择性靶向特定 MMP 或 ADAM 的 MP 抑制剂的重要性。还回顾了用于开发新型 MP 抑制剂和 MP 响应药物递送工具的最新进展和技术。