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自噬介导靶向降解,一种有前途的药物开发策略。

Autophagy mediated targeting degradation, a promising strategy in drug development.

机构信息

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, PR China.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, PR China.

出版信息

Bioorg Chem. 2024 Aug;149:107466. doi: 10.1016/j.bioorg.2024.107466. Epub 2024 May 20.

Abstract

Targeted protein degradation (TPD) technologies have become promising therapeutic approaches through degrading disease-causing proteins via the protein degradation system. Autophagy is a fundamental biological process with a high relationship to protein degradation, which belongs to one of two main protein degradation pathways, the autophagy-lysosomal system. Recently, various autophagy-based TPD techniques ATTECs, AUTACs, and AUTOTACs, etc, have also been gradually developed, and they have achieved efficient degradation potency for the targeted protein, expanding the potential of degradation for large-size proteins or protein aggregates. Herein, we introduce the machinery of autophagy and its relation to protein degradation, and multiple methods for using autophagy to specifically degrade target proteins.

摘要

靶向蛋白降解(TPD)技术通过蛋白降解系统降解致病蛋白,已成为一种很有前途的治疗方法。自噬是一种基本的生物学过程,与蛋白降解关系密切,属于两种主要的蛋白降解途径之一,即自噬溶酶体系统。最近,各种基于自噬的 TPD 技术 ATTECs、AUTACs 和 AUTOTACs 等也逐渐得到发展,它们对靶向蛋白具有高效的降解能力,扩大了对大尺寸蛋白或蛋白聚集体的降解潜力。本文介绍了自噬的机制及其与蛋白降解的关系,以及利用自噬特异性降解靶蛋白的多种方法。

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