PDF(Pubmed)
Abstract：
Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer\'s disease, Parkinson\'s disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.
摘要：
蛋白酪氨酸磷酸酶1B（PTP1B）的过表达会破坏信号通路并导致许多人类疾病。特别是,它在代谢紊乱（I型和II型糖尿病，脂肪肝,和肥胖)；神经退行性疾病(阿尔茨海默病，帕金森病）；重度抑郁症；钙化性主动脉瓣疾病；以及几种癌症类型。鉴于这众多的治疗应用，在鉴定PTP1B及其作用后不久，开始寻求引入安全和选择性的酶抑制剂。遗憾的是,迄今为止所做的努力被证明是不成功的，由于所有提出的PTP1B抑制剂都失败了，或尚未完成，临床试验。旨在帮助引入新一代PTP1B抑制剂，这项工作收集和组织当前的艺术状态。特别是,这篇综述旨在阐明与PTP1B过表达相关的许多疾病之间的复杂关系，因为我们认为，在处理相互关联的疾病时，建立和遵循全新的整体方法至关重要。考虑到这一点，这篇全面的综述旨在验证PTP1B酶作为一种有前途的分子靶标，并加强这一方向的未来研究。
