Zhai Mingzhu, Hu Haibei, Zheng Yi, Wu Benqing, Sun Wuping
Center for Medical Experiments (CME), University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, China.
Yantian Hospital, Southern University of Science and Technology, Shenzhen, China.
Ther Adv Neurol Disord. 2023 Mar 25;16:17562864231163361. doi: 10.1177/17562864231163361. eCollection 2023.
Chemotherapy-induced peripheral neuropathy (CIPN)-mediated paresthesias are a common complication in cancer patients undergoing chemotherapy. There are currently no treatments available to prevent or reverse CIPN. Therefore, new therapeutic targets are urgently needed to develop more effective analgesics. However, the pathogenesis of CIPN remains unclear, and the prevention and treatment strategies of CIPN are still unresolved issues in medicine. More and more studies have demonstrated that mitochondrial dysfunction has become a major factor in promoting the development and maintenance of CIPN, and peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC1α) plays a significant role in maintaining the mitochondrial function, protecting peripheral nerves, and alleviating CIPN. In this review, we highlight the core role of PGC1α in regulating oxidative stress and maintaining normal mitochondrial function and summarize recent advances in its therapeutic effects and mechanisms in CIPN and other forms of peripheral neuropathy. Emerging studies suggest that PGC1α activation may positively impact CIPN mitigation by modulating oxidative stress, mitochondrial dysfunction, and inflammation. Therefore, novel therapeutic strategies targeting PGC1α could be a potential therapeutic target in CIPN.
化疗引起的周围神经病变（CIPN）介导的感觉异常是接受化疗的癌症患者常见的并发症。目前尚无预防或逆转CIPN的治疗方法。因此，迫切需要新的治疗靶点来开发更有效的镇痛药。然而，CIPN的发病机制仍不清楚，CIPN的预防和治疗策略仍是医学上未解决的问题。越来越多的研究表明，线粒体功能障碍已成为促进CIPN发生和维持的主要因素，过氧化物酶体增殖物激活受体γ（PPARγ）辅激活因子1α（PGC1α）在维持线粒体功能、保护周围神经和减轻CIPN方面发挥着重要作用。在这篇综述中，我们强调了PGC1α在调节氧化应激和维持正常线粒体功能中的核心作用，并总结了其在CIPN和其他形式周围神经病变中的治疗作用及机制的最新进展。新出现的研究表明，激活PGC1α可能通过调节氧化应激、线粒体功能障碍和炎症对减轻CIPN产生积极影响。因此，针对PGC1α的新型治疗策略可能是CIPN的潜在治疗靶点。
