靶向蛋白酪氨酸磷酸酶在肝脏疾病中的治疗潜力
Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases
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影响因子:14.6
分区:医学1区 Top / 药学1区
发表日期:2024 Aug
作者:
Ao Wang, Yi Zhang, Xinting Lv, Guang Liang
DOI:
10.1016/j.apsb.2024.05.006
摘要
蛋白酪氨酸磷酸化是一种调节蛋白质结构的翻译后修饰，参与调控生物体的稳态和功能。此生理过程由蛋白酪氨酸激酶（PTKs）和蛋白酪氨酸磷酸酶（PTPs）两个酶家族调控。作为蛋白质功能的重要调节因子，PTPs在维持细胞固有生理功能及肝脏的生理和病理过程中不可或缺。PTP的失调与多种肝脏疾病有关，包括慢性肝病（CLDs）、肝细胞癌（HCC）和肝损伤，部分PTPs正成为药物治疗的潜在靶点。因此，系统整理PTPs的功能与机制显得尤为必要。同时，结合当前靶向治疗的研究状态，强调几种在肝病发生发展中具有临床意义的PTP成员。作为肝病治疗的新兴突破方向，本文总结了PTP靶向化合物在肝病中的研究现状，旨在展现其临床潜力。总体目标是推动新型PTP基础的肝病治疗路径的开发。
Abstract
Protein tyrosine phosphorylation is a post-translational modification that regulates protein structure to modulate demic organisms' homeostasis and function. This physiological process is regulated by two enzyme families, protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). As an important regulator of protein function, PTPs are indispensable for maintaining cell intrinsic physiology in different systems, as well as liver physiological and pathological processes. Dysregulation of PTPs has been implicated in multiple liver-related diseases, including chronic liver diseases (CLDs), hepatocellular carcinoma (HCC), and liver injury, and several PTPs are being studied as drug therapeutic targets. Therefore, given the regulatory role of PTPs in diverse liver diseases, a collated review of their function and mechanism is necessary. Moreover, based on the current research status of targeted therapy, we emphasize the inclusion of several PTP members that are clinically significant in the development and progression of liver diseases. As an emerging breakthrough direction in the treatment of liver diseases, this review summarizes the research status of PTP-targeting compounds in liver diseases to illustrate their potential in clinical treatment. Overall, this review aims to support the development of novel PTP-based treatment pathways for liver diseases.