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翻译后修饰与糖尿病。

Post-Translational Modifications and Diabetes.

机构信息

Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USA.

Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, USA.

出版信息

Biomolecules. 2024 Mar 6;14(3):310. doi: 10.3390/biom14030310.

Abstract

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, and SUMOylation, play important roles in diabetes and its pathological consequences. Therefore, the investigation of these PTMs not only sheds important light on the mechanistic regulation of diabetes but also opens new avenues for targeted therapies. Here, we offer a comprehensive overview of the role of several PTMs in diabetes, focusing on the most recent advances in understanding their functions and regulatory mechanisms. Additionally, we summarize the pharmacological interventions targeting PTMs that have advanced into clinical trials for the treatment of diabetes. Current challenges and future perspectives are also provided.

摘要

糖尿病及其相关并发症已日益成为全球医疗保健的重大挑战。目前的治疗策略包括 1 型糖尿病(T1D)的胰岛素替代疗法和 2 型糖尿病(T2D)的小分子药物。尽管取得了这些进展,但糖尿病的复杂性需要创新的临床干预措施来进行有效治疗和并发症预防。累积的证据表明,蛋白质翻译后修饰(PTMs),包括糖基化、磷酸化、乙酰化和 SUMO 化,在糖尿病及其病理后果中发挥着重要作用。因此,研究这些 PTMs 不仅为糖尿病的机制调控提供了重要的启示,也为靶向治疗开辟了新的途径。在这里,我们全面概述了几种 PTMs 在糖尿病中的作用,重点介绍了理解它们功能和调控机制的最新进展。此外,我们还总结了针对 PTMs 的药理学干预措施,这些措施已进入糖尿病治疗的临床试验阶段。还提供了当前的挑战和未来的展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8056/10968569/ccdcb2b6953b/biomolecules-14-00310-g001.jpg

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