Abstract:
Autophagy is an intracellular recycling process that maintains cellular homeostasis by degrading excess or defective macromolecules and organelles. Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy in which a substrate containing a KFERQ-like motif is recognized by a chaperone protein, delivered to the lysosomal membrane, and then translocated to the lysosome for degradation with the assistance of lysosomal membrane protein 2A. Normal CMA activity is involved in the regulation of cellular proteostasis, metabolism, differentiation, and survival. CMA dysfunction disturbs cellular homeostasis and directly participates in the pathogenesis of human diseases. Previous investigations on CMA in the central nervous system have primarily focus on neurodegenerative diseases, such as Parkinson\'s disease and Alzheimer\'s disease. Recently, mounting evidence suggested that brain injuries involve a wider range of types and severities, making the involvement of CMA in the bidirectional processes of damage and repair even more crucial. In this review, we summarize the basic processes of CMA and its associated regulatory mechanisms and highlight the critical role of CMA in brain injury such as cerebral ischemia, traumatic brain injury, and other specific brain injuries. We also discuss the potential of CMA as a therapeutic target to treat brain injury and provide valuable insights into clinical strategies.
摘要:
自噬是通过降解过量或缺陷的大分子和细胞器来维持细胞内稳态的细胞内再循环过程。伴侣介导的自噬(CMA)是一种高度选择性的自噬形式,其中含有KFERQ样基序的底物被伴侣蛋白识别。传递到溶酶体膜,然后在溶酶体膜蛋白2A的帮助下转移到溶酶体中进行降解。正常的CMA活性参与细胞蛋白质停滞的调节,新陈代谢,分化,和生存。CMA功能障碍扰乱细胞稳态并直接参与人类疾病的发病机制。以前对中枢神经系统CMA的研究主要集中在神经退行性疾病上,如帕金森病和阿尔茨海默病。最近,越来越多的证据表明,脑损伤涉及更广泛的类型和严重程度,使CMA参与损伤和修复的双向过程更加关键。在这次审查中,本文总结了CMA的基本过程及其相关调控机制,并强调了CMA在脑缺血等脑损伤中的重要作用,创伤性脑损伤,和其他特定的脑损伤。我们还讨论了CMA作为治疗脑损伤的治疗靶点的潜力,并为临床策略提供了有价值的见解。