Yu Qian, Li Li, Yu Shuyi, Han Jialin, Cheng Qian, Cui Zhikang, Chen Hang, Li Ming, Lu Zhiming
Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Afliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.
Neurochem Res. 2025 Jul 28;50(4):251. doi: 10.1007/s11064-025-04490-z.
Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive neurodegeneration and a variety of cognitive deficits. Of note, mitochondrial malfunctions occur early in the disease's development. Mitophagy impairment leads to the build-up of damaged mitochondria inside the cells, causing malfunction and eventual death of the cells. This review summarizes the mechanisms linking mitochondrial damage and autophagy dysregulation to AD and highlights potential therapeutic opportunities. We summarize how mitochondrial dysfunction contributes to AD, including defects in mitochondrial biogenesis, impaired dynamics, the impact of AD-related protein aggregates on mitochondrial integrity, and defective axonal transport. We also explore the roles of mitophagy in AD, including its function in the removal of harmed proteins and organelles. Finally, we highlight the therapeutic strategies for the treatment of AD, targeting molecular components involved in mitochondrial damage and autophagy dysregulation in AD, i.e., antioxidants, mitochondrial modulators, and mitophagy enhancers.
阿尔茨海默病（AD）是一种神经退行性疾病，会导致进行性神经变性和多种认知缺陷。值得注意的是，线粒体功能障碍在该疾病发展的早期就会出现。线粒体自噬受损会导致细胞内受损线粒体的积累，从而引起细胞功能异常并最终导致细胞死亡。本综述总结了将线粒体损伤和自噬失调与AD联系起来的机制，并强调了潜在的治疗机会。我们总结了线粒体功能障碍如何导致AD，包括线粒体生物发生缺陷、动力学受损、AD相关蛋白聚集体对线粒体完整性的影响以及轴突运输缺陷。我们还探讨了线粒体自噬在AD中的作用，包括其在清除受损蛋白质和细胞器方面的功能。最后，我们强调了针对AD的治疗策略，这些策略靶向参与AD中线粒体损伤和自噬失调的分子成分，即抗氧化剂、线粒体调节剂和线粒体自噬增强剂。
