摘要
脯氨酰异构酶Pin1是一种独特的酶,它将pSer/pThr与脯氨酸之间的顺反构象异构化,从而调节其靶蛋白的功能、稳定性和/或亚细胞分布。Pin1的这种调控作用涉及多种生理功能以及多种疾病的致病机制。值得注意的是,Pin1缺乏或失活是阿尔茨海默病的潜在原因,因为Pin1诱导Tau的降解。相比之下,Pin1过表达与肿瘤恶性程度高度相关,因为Pin1控制了许多癌基因和抑癌基因。因此,Pin1抑制剂作为抗癌药物已经被开发出来。有趣的是,最近密集的研究已经证实Pin1与非酒精性脂肪变性、肥胖、动脉粥样硬化、肺纤维化、心力衰竭等的发生或发展有关,所有这些都是在Pin1缺陷小鼠中实验诱导的。本文综述了Pin1抑制剂在包括恶性肿瘤在内的多种疾病中的应用前景,并介绍了近年来Pin1抑制剂的研究进展。
关键词: 脯氨酰异构酶Pin1
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