The critical role of the endolysosomal system in cerebral ischemia  

作　　者：Hui-Yi Zhang Ye Tian Han-Yan Shi Ya Cai Ying Xu 

机构地区：[1]Department of Anesthesiology,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China [2]Department of Orthopedics,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China

出　　处：《Neural Regeneration Research》2023年第5期983-990,共8页中国神经再生研究（英文版）

基　　金：supported the National Natural Science Foundation of China,No. 81970760 (to YT);the Natural Science Foundation of Liaoning Province,No. 2021-MS-201 (to YX);the 345 Talent Project of Shengjing Hospital of China Medical University,No. M0370 (to YT);the 345 Talent Project of Shengjing Hospital of China Medical University,No. M0395 (to YX)。

摘　　要：Cerebral ischemia is a serious disease that triggers sequential pathological mechanisms, leading to significant morbidity and mortality. Although most studies to date have typically focused on the lysosome, a single organelle, current evidence supports that the function of lysosomes cannot be separated from that of the endolysosomal system as a whole. The associated membrane fusion functions of this system play a crucial role in the biodegradation of cerebral ischemia-related products. Here, we review the regulation of and the changes that occur in the endolysosomal system after cerebral ischemia, focusing on the latest research progress on membrane fusion function. Numerous proteins, including N-ethylmaleimide-sensitive factor and lysosomal potassium channel transmembrane protein 175, regulate the function of this system. However, these proteins are abnormally expressed after cerebral ischemic injury, which disrupts the normal fusion function of membranes within the endolysosomal system and that between autophagosomes and lysosomes. This results in impaired “maturation” of the endolysosomal system and the collapse of energy metabolism balance and protein homeostasis maintained by the autophagy-lysosomal pathway. Autophagy is the final step in the endolysosomal pathway and contributes to maintaining the dynamic balance of the system. The process of autophagosome-lysosome fusion is a necessary part of autophagy and plays a crucial role in maintaining energy homeostasis and clearing aging proteins. We believe that, in cerebral ischemic injury, the endolysosomal system should be considered as a whole rather than focusing on the lysosome. Understanding how this dynamic system is regulated will provide new ideas for the treatment of cerebral ischemia.

关 键 词：AUTOPHAGY biodegradation brain injury chaperone-mediated autophagy endolysosomal system fusion HYPOXIA-ISCHEMIA brain mitophagy N-ethylmaleimide-sensitive protein TMEM175 

分 类 号：R743.31[医药卫生—神经病学与精神病学]