摘要
背景:基质金属蛋白酶(MMPs),也称为金属蛋白酶,是一种降解蛋白质的酶,需要活性金属原子的存在。有20多种类型的MMP,它们通过细胞外基质的蛋白水解降解促进细胞迁移。MMPs在癌症和炎症区域上调。MMPs有三个保护区:亲MMP、催化和血友病。通过这些结构域,MMPs切割基质和细胞-细胞屏障。因此,MMPs切割整个细胞外基质(ECM)。换句话说,它们分解大部分与ECM相关的成分,在体内细胞和病理生理事件中扮演关键酶的角色。 简介:在各种疾病的进展中,含Zn2+的内型肽酶直接降解和重塑ECM区域。MMPs常见于炎症反应、牙周病变、炎症性肺损伤、动脉硬化性平滑肌、关节炎以及肿瘤转移和侵袭的异常疾病状态。众所周知,它们还通过破坏真皮中的胶原蛋白参与衰老过程,如皱纹形成。特别是,通过MMP依赖性炎症反应的疾病的发生是由ECM和基底膜区域(细胞的支撑结构)中的蛋白质分解引起的。 方法:本文综述了过去20年来,在结构重塑、底物识别特异性和药理学适用性方面,对与各种人类疾病相关的MMP的通用和选择性抑制剂的研究进展。 结果:在两种类似类型的MMP中,MMP-2被称为明胶酶A,具有72kDa,而MMP-9被称为明胶酶B,具有92kDa。这两者在这一行动中都起着关键作用。因此,两种酶的表达水平在疾病的发病和发展过程中一致。基质金属蛋白酶的内源性组织抑制剂(TIMPs)对每种MMP抑制剂类型都具有高度特异性。内在因素通过抑制MMP依赖性或独立性炎症反应介导的各种疾病的发作来调节各种MMP类型。TIMP1和TIMP2分别选择性地抑制与炎症反应相关的疾病预后相关的MMP-9和MMP-2酶活性。MMP介导的疾病的主要发病机制与各种人体组织中炎性细胞的增殖有关,这表明其诊断或治疗这些疾病的潜力。发现一种抑制MMPs的物质对于预防和治疗各种MMP依赖性疾病非常重要。 结论:大量研究已经对MMP抑制剂进行了研究,但其中大多数是合成化合物。使用天然产物作为MMP抑制剂的研究最近才成为人们感兴趣的主题。本文就基质金属蛋白酶的生理特性、功能和治疗药物的研究进展进行综述。
关键词: 基质金属蛋白酶(MMP),MMP-9,MMP介导的发病机制,炎症,MMP抑制剂,ECM区域。
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