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癌症与蛋白质构象紊乱中的自噬。

Autophagy in cancer and protein conformational disorders.

作者信息

Attanasio Sergio

机构信息

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

FEBS Lett. 2025 Aug;599(16):2250-2271. doi: 10.1002/1873-3468.70061. Epub 2025 May 8.

Abstract

Autophagy is a catabolic process by which cells maintain cellular homeostasis through the degradation of dysfunctional cytoplasmic components, such as toxic misfolded proteins and damaged organelles, within the lysosome. It is a multistep process that is tightly regulated by nutrient, energy, and stress-sensing mechanisms. Autophagy plays a pivotal role in various biological processes, including protein and organelle quality control, defense against pathogen infections, cell metabolism, and immune surveillance. As a result, autophagy dysfunction is linked to a variety of pathological conditions. The role of autophagy in cancer is complex and dynamic. Depending on the context, autophagy can have both tumor-suppressive and pro-tumorigenic effects. In contrast, its role is more clearly defined in protein conformational disorders, where autophagy serves as a mechanism to reduce toxic protein aggregation, thereby improving cellular homeostasis. Because autophagy-based therapies hold promising potential for the treatment of cancer and protein conformational disorders, this review will highlight the latest findings and advancements in these areas.

摘要

自噬是一种分解代谢过程,通过该过程细胞在溶酶体内降解功能失调的细胞质成分(如有毒的错误折叠蛋白和受损细胞器)来维持细胞内稳态。它是一个多步骤过程,受到营养、能量和应激感应机制的严格调控。自噬在各种生物学过程中发挥关键作用,包括蛋白质和细胞器质量控制、抵御病原体感染、细胞代谢和免疫监视。因此,自噬功能障碍与多种病理状况相关。自噬在癌症中的作用复杂且具有动态性。根据具体情况,自噬既可以具有肿瘤抑制作用,也可以具有促肿瘤发生作用。相比之下,其在蛋白质构象紊乱中的作用更为明确,在这种情况下自噬作为一种减少有毒蛋白质聚集的机制,从而改善细胞内稳态。由于基于自噬的疗法在癌症和蛋白质构象紊乱治疗方面具有广阔前景,本综述将重点介绍这些领域的最新发现和进展。

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