Shefa Ulfuara, Jeong Na Young, Song In Ok, Chung Hyung-Joo, Kim Dokyoung, Jung Junyang, Huh Youngbuhm
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, South Korea.
Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan, South Korea.
Neural Regen Res. 2019 May;14(5):749-756. doi: 10.4103/1673-5374.249218.
Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.
线粒体自噬可由多种刺激激活，包括缺氧、能量应激和氧化磷酸化活性增加。线粒体自噬与氧化应激条件和中枢神经退行性疾病有关。线粒体自噬的适当调节对于维持体内平衡至关重要；相反，通过线粒体自噬对线粒体的清除不足会导致包括活性氧和活性氮在内的氧化物质的产生，从而引发各种神经退行性疾病，如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症。这些疾病在老年人中最为普遍，他们的身体无法维持适当的线粒体自噬功能来对抗氧化物质。由于线粒体自噬对正常身体功能至关重要，通过靶向线粒体自噬途径，我们可以改善这些疾病状况。寻找治疗这些疾病状况的有效疗法是一个持续的过程，这就是为什么需要更多研究的原因。此外，更多相关研究有助于建立目前急需的治疗条件。在这篇综述中，我们讨论了线粒体自噬如何在体内平衡中发挥重要作用，以及其失调如何导致神经退行性变。我们还讨论了对抗氧化物质和靶向线粒体自噬如何有助于治疗这些神经退行性疾病。
