溶酶体在作为其最终目的地的各种细胞内途径中起着至关重要的作用。各种压力源,无论是轻度还是重度,可以诱导溶酶体膜透化(LMP),导致溶酶体酶释放到细胞质中。LMP不仅在各种细胞事件中起关键作用,而且还显着有助于程序性细胞死亡(PCD)。先前的研究表明LMP参与中枢神经系统(CNS)损伤,包括创伤性脑损伤(TBI),脊髓损伤(SCI),蛛网膜下腔出血(SAH),和缺氧缺血性脑病(HIE)。然而,LMP在CNS损伤中的潜在机制尚不清楚.LMP的发生导致炎症通路的激活,氧化应激水平升高,和PCD。在这里,我们全面概述了有关LMP的最新发现,并强调了其在细胞事件和PCDs(溶酶体依赖性细胞死亡,凋亡,焦亡,铁性凋亡,和自噬)。此外,通过总结和探索最新的进展,我们巩固了LMP在中枢神经系统损伤中的最新见解.我们还回顾了潜在的治疗策略,旨在保留LMP或抑制溶酶体中酶的释放,以减轻LMP在CNS损伤中的后果。更好地了解LMP在CNS损伤中的作用可能有助于开发CNS损伤的战略治疗方案。
Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also
review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.