Mandal Malay, Mandal Amritlal, Das Sudip, Chakraborti Tapati, Sajal Chakraborti
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India.
Mol Cell Biochem. 2003 Oct;252(1-2):305-29. doi: 10.1023/a:1025526424637.
Matrix metalloproteinases (MMPs) are a family of neutral proteinases that are important for normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, pulmonary fibrosis, emphysema and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood brain barrier and to contribute to the neuroinflammatory responses in many neurological diseases. Inhibition of MMPs have been shown to prevent progression of these diseases. Currently, certain MMP inhibitors have entered into clinical trials. A goal to the future should be to design selective synthetic inhibitors of MMPs that have minimum side effects. MMP inhibitors are designed in such a way that these can not only bind at the active site of the proteinases but also to have the characteristics to bind to other sites of MMPs which might be a promising route for therapy. To name a few: catechins, a component isolated from green tea; and Novastal, derived from extracts of shark cartilage are currently in clinical trials for the treatment of MMP-mediated diseases.
基质金属蛋白酶(MMPs)是一类中性蛋白酶,对正常发育、伤口愈合以及多种病理过程至关重要,这些病理过程包括转移性癌细胞的扩散、关节的关节炎性破坏、动脉粥样硬化、肺纤维化、肺气肿和神经炎症。在中枢神经系统(CNS)中,MMPs已被证明可降解基膜成分,导致血脑屏障破坏,并在许多神经疾病中促成神经炎症反应。已证明抑制MMPs可预防这些疾病的进展。目前,某些MMP抑制剂已进入临床试验。未来的一个目标应该是设计出副作用最小的MMPs选择性合成抑制剂。MMP抑制剂的设计方式使其不仅能结合蛋白酶的活性位点,还具有结合MMPs其他位点的特性,这可能是一条有前景的治疗途径。仅举几例:儿茶素,一种从绿茶中分离出的成分;以及源自鲨鱼软骨提取物的Novastal,目前正处于治疗MMP介导疾病的临床试验中。