Department of Orthopaedic Surgery, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan.
Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Cells. 2022 Apr 2;11(7):1205. doi: 10.3390/cells11071205.
Autophagy is an important function that mediates the degradation of intracellular proteins and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and is involved in the pathogenic process of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Previous studies have suggested that the activation of CMA to degrade aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that CMA activity is upregulated in damaged neural tissue following acute neurological insults, such as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested that various protein degradation mechanisms are important for removing toxic aberrant proteins associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but also in acute neurological insults. We herein review current knowledge concerning the biological mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic strategies for effective treatments.
自噬是一种重要的功能，介导细胞内蛋白质和细胞器的降解。伴侣介导的自噬（CMA）降解选定的蛋白质，并在各种生理和病理条件下对细胞蛋白质稳态具有关键作用。CMA 功能障碍导致中枢神经系统（CNS）中有毒蛋白质聚集体的积累，并参与包括帕金森病和阿尔茨海默病在内的神经退行性疾病的发病过程。先前的研究表明，激活 CMA 以降解异常蛋白质可以在 CNS 中提供神经保护作用。最近的研究表明，在急性神经损伤（如脑梗死、创伤性脑损伤和脊髓损伤）后，受损神经组织中的 CMA 活性上调。还表明，各种蛋白质降解机制对于去除与 CNS 中急性神经损伤后的继发性损伤相关的有毒异常蛋白质很重要。因此，增强 CMA 途径不仅可以在神经退行性疾病中，而且可以在急性神经损伤中诱导神经保护作用。我们在此综述了与 CMA 相关的生物学机制的现有知识，并强调了 CMA 在神经退行性疾病和急性神经损伤中的作用。我们还讨论了开发 CMA 靶向治疗策略的可能性，以实现有效的治疗。
