Swerdlow Natalie S, Wilkins Heather M
University of Kansas Alzheimer's Disease Center, University of Kansas, Kansas City, KS 66160, USA.
Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Int J Mol Sci. 2020 Dec 18;21(24):9661. doi: 10.3390/ijms21249661.
Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Mitophagy is a form of macroautophagy, were mitochondria and their contents are ubiquitinated, engulfed, and removed through lysosome degradation. Recent studies have implicated mitophagy dysregulation in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.
应激机制长期以来一直与神经元丢失和神经退行性疾病相关。细胞应激和神经元丢失的起源可能源于多种途径。这些途径包括（但不限于）生物能量衰竭、神经炎症和蛋白质稳态丧失。细胞具有适应性补偿机制来克服应激并避免死亡。其中一种机制是线粒体自噬。线粒体自噬是一种巨自噬形式，线粒体及其内容物被泛素化，通过溶酶体降解被吞噬并清除。最近的研究表明线粒体自噬失调与几种神经退行性疾病有关，目前正在进行针对线粒体自噬途径的临床试验。在此，我们综述线粒体自噬途径、线粒体自噬在神经退行性变中的作用、潜在治疗方法以及进一步研究的必要性。
