CHIP与衰老：蛋白质稳态和细胞衰老的关键调节因子。

CHIP and aging: a key regulator of proteostasis and cellular senescence.

作者信息

Pandey Surya Nath, Agrawal Neetu, Moglad Ehssan, Priya G Padma, Srivastava Manish, Chennakesavulu Kattela, Mohanty Biswaranjan, Arya Renu, Kazmi Imran, I Alzarea Sami, Almalk Waleed Hassan, Goyal Kavita

机构信息

Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Uttar Pradesh, Moradabad, 244001, India.

Institute of Pharmaceutical Research, GLA University, Uttar Pradesh, Mathura, India.

出版信息

Biogerontology. 2025 May 5;26(3):104. doi: 10.1007/s10522-025-10247-6.

DOI:10.1007/s10522-025-10247-6

PMID:40323531

Abstract

Degradation of proteostasis, mitochondrial function, and cellular stress resistance results in a build-up of damaged proteins, oxidative insult, and chronic inflammation, characteristic of aging. CHIP is essential for maintaining protein quality control and cellular homeostasis by having dual E3 ubiquitin ligase and co-chaperone activities. CHIP facilitates proteostasis by maintaining proteostasis in misfolded, aggregated proteins by promoting their degradation. Mitochondrial dysfunction, oxidative imbalance, and cellular senescence are caused by its age-associated decline and contribute to neurodegenerative, cardiovascular, and oncogenic disease pathogenesis. Examples of recent pharmacological and gene-based strategies to correct CHIP and restore stress resilience have been made. This review examines the multiple facets of the aging role of CHIP and its potential as an aging disease therapy target.

摘要

蛋白质稳态、线粒体功能及细胞应激抗性的退化会导致受损蛋白质的积累、氧化损伤和慢性炎症，这些都是衰老的特征。CHIP通过具有双E3泛素连接酶和共伴侣活性，对于维持蛋白质质量控制和细胞内稳态至关重要。CHIP通过促进错误折叠、聚集蛋白质的降解来维持其蛋白质稳态，从而促进整体蛋白质稳态。其与年龄相关的下降会导致线粒体功能障碍、氧化失衡和细胞衰老，并促成神经退行性疾病、心血管疾病和肿瘤发生的发病机制。最近已经有了纠正CHIP并恢复应激恢复力的基于药理学和基因的策略实例。本综述探讨了CHIP在衰老过程中作用的多个方面及其作为衰老疾病治疗靶点的潜力。