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蛋白酪氨酸磷酸酶1B在代谢性疾病和心血管疾病中的作用:从机制到治疗

Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.

作者信息

Sun Yan, Dinenno Frank A, Tang Peiyang, Kontaridis Maria I

机构信息

Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, NY, United States.

Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, United States.

出版信息

Front Cardiovasc Med. 2024 Aug 22;11:1445739. doi: 10.3389/fcvm.2024.1445739. eCollection 2024.

Abstract

Protein Tyrosine Phosphatase 1B (PTP1B) has emerged as a significant regulator of metabolic and cardiovascular disease. It is a non-transmembrane protein tyrosine phosphatase that negatively regulates multiple signaling pathways integral to the regulation of growth, survival, and differentiation of cells, including leptin and insulin signaling, which are critical for development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Given PTP1B's central role in glucose homeostasis, energy balance, and vascular function, targeted inhibition of PTP1B represents a promising strategy for treating these diseases. However, challenges, such as off-target effects, necessitate a focus on tissue-specific approaches, to maximize therapeutic benefits while minimizing adverse outcomes. In this review, we discuss molecular mechanisms by which PTP1B influences metabolic and cardiovascular functions, summarize the latest research on tissue-specific roles of PTP1B, and discuss the potential for PTP1B inhibitors as future therapeutic agents.

摘要

蛋白酪氨酸磷酸酶1B(PTP1B)已成为代谢和心血管疾病的重要调节因子。它是一种非跨膜蛋白酪氨酸磷酸酶,对细胞生长、存活和分化调节所必需的多种信号通路起负调节作用,包括瘦素和胰岛素信号通路,这些信号通路对肥胖、胰岛素抵抗、2型糖尿病和心血管疾病的发生发展至关重要。鉴于PTP1B在葡萄糖稳态、能量平衡和血管功能中的核心作用,靶向抑制PTP1B是治疗这些疾病的一种有前景的策略。然而,诸如脱靶效应等挑战使得有必要专注于组织特异性方法,以在使不良后果最小化的同时最大化治疗益处。在本综述中,我们讨论了PTP1B影响代谢和心血管功能的分子机制,总结了关于PTP1B组织特异性作用的最新研究,并讨论了PTP1B抑制剂作为未来治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/11374623/f8f192696a94/fcvm-11-1445739-g001.jpg

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