Yang Xiong, Zhang Yu, Luo Jia-Xin, Zhu Tao, Ran Zhao, Mu Ben-Rong, Lu Mei-Hong
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3503-3528. doi: 10.1007/s00210-023-02636-w. Epub 2023 Aug 3.
Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.
线粒体是神经细胞至关重要的能量来源。线粒体网络还作为一种防御机制，抵御可能威胁神经系统稳定性的外部应激源。然而，受损线粒体的过度积累会导致神经元死亡。线粒体自噬是线粒体质量控制系统中的一条重要途径，可通过选择性清除受损线粒体来保护神经元。在大多数神经疾病中，功能失调的线粒体是一个常见特征，靶向线粒体自噬的药物可改善症状。在此，我们综述了线粒体自噬在阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、亨廷顿舞蹈病、中风和创伤性脑损伤中的作用。我们还总结了促进线粒体自噬的药物和非药物方法，并描述了它们在神经疾病中的治疗作用，以便为可用于神经疾病治疗的潜在治疗药物提供有价值的见解。然而，大多数关于线粒体自噬调节的研究基于使用细胞和动物模型的临床前研究，这可能无法准确反映对人类的影响。这给靶向线粒体自噬的药物的临床应用带来了挑战。此外，这些药物可能存在难以耐受的副作用和毒性风险。未来的研究应聚焦于开发更安全、更具针对性的线粒体自噬药物。
