Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology,Pharmacological Reviews

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Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2022-07-01 , DOI: 10.1124/pharmrev.121.000349
Luiz G N de Almeida ₁ , Hayley Thode ₁ , Yekta Eslambolchi ₁ , Sameeksha Chopra ₁ , Daniel Young ₁ , Sean Gill ₁ , Laurent Devel ₁ , Antoine Dufour ₂

Affiliation

The first matrix metalloproteinase (MMP) was discovered in 1962 from the tail of a tadpole by its ability to degrade collagen. As their name suggests, matrix metalloproteinases are proteases capable of remodeling the extracellular matrix. More recently, MMPs have been demonstrated to play numerous additional biologic roles in cell signaling, immune regulation, and transcriptional control, all of which are unrelated to the degradation of the extracellular matrix. In this review, we will present milestones and major discoveries of MMP research, including various clinical trials for the use of MMP inhibitors. We will discuss the reasons behind the failures of most MMP inhibitors for the treatment of cancer and inflammatory diseases. There are still misconceptions about the pathophysiological roles of MMPs and the best strategies to inhibit their detrimental functions. This review aims to discuss MMPs in preclinical models and human pathologies. We will discuss new biochemical tools to track their proteolytic activity in vivo and ex vivo, in addition to future pharmacological alternatives to inhibit their detrimental functions in diseases.

中文翻译：

基质金属蛋白酶：从分子机制到生理学、病理生理学和药理学

第一个基质金属蛋白酶 (MMP) 是在 1962 年从蝌蚪的尾巴中发现的，因为它具有降解胶原蛋白的能力。顾名思义，基质金属蛋白酶是能够重塑细胞外基质的蛋白酶。最近，MMP 已被证明在细胞信号传导、免疫调节和转录控制中发挥许多额外的生物学作用，所有这些都与细胞外基质的降解无关。在这篇综述中，我们将介绍 MMP 研究的里程碑和主要发现，包括使用 MMP 抑制剂的各种临床试验。我们将讨论大多数 MMP 抑制剂在治疗癌症和炎症性疾病方面失败的原因。关于 MMP 的病理生理作用以及抑制其有害功能的最佳策略仍然存在误解。本综述旨在讨论临床前模型和人类病理学中的 MMP。我们将讨论新的生化工具，以跟踪它们在体内和体外的蛋白水解活性，以及未来抑制它们在疾病中的有害功能的药理学替代品。

更新日期：2022-06-23

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