Gemingnuer Ahequeli, Yin Rui, Liu Yan, Tian Yuan, Meng Xin
School of Pharmacy, Heilongjiang University of Chinese Medicine, NO 24 Heping Road, 150040, Harbin, P. R. China.
Mol Biol Rep. 2025 Sep 10;52(1):881. doi: 10.1007/s11033-025-10997-z.
Lysosome-dependent cell death (LDCD) is a regulated form of cell death initiated by increased lysosomal membrane permeability, leading to the cytoplasmic release of lysosomal enzymes and subsequent cellular damage. Molecular mechanisms controlling LDCD include lysosomal membrane instability and lysosomal enzyme release, which together lead to cell damage. A more profound comprehension of these underlying mechanisms may reveal new therapeutic targets for diseases associated with lysosomal dysfunction. This crucial process is implicated in numerous pathological conditions, including neurodegenerative diseases, various types of cancer, cardiovascular disorders, and autoimmune diseases. Despite the considerable therapeutic implications of LDCD, recent years have witnessed a notable absence of comprehensive reviews addressing the exploration of LDCD-related therapeutic targets in disease management. This review systematically discusses the molecular pathways of LDCD, its role in disease pathogenesis, potential clinical biomarkers, and therapeutic interventions. This extensive endeavor aims to establish a robust foundation for researchers to explore the complexities of LDCD in greater depth and to propel drug discovery in this highly promising field.
溶酶体依赖性细胞死亡(LDCD)是一种由溶酶体膜通透性增加引发的程序性细胞死亡形式,导致溶酶体酶释放到细胞质中并随后造成细胞损伤。控制LDCD的分子机制包括溶酶体膜不稳定和溶酶体酶释放,二者共同导致细胞损伤。对这些潜在机制更深入的理解可能会揭示与溶酶体功能障碍相关疾病的新治疗靶点。这一关键过程涉及多种病理状况,包括神经退行性疾病、各类癌症、心血管疾病和自身免疫性疾病。尽管LDCD具有相当大的治疗意义,但近年来明显缺乏全面综述探讨在疾病管理中对LDCD相关治疗靶点的探索。本综述系统地讨论了LDCD的分子途径、其在疾病发病机制中的作用、潜在的临床生物标志物以及治疗干预措施。这一广泛努力旨在为研究人员更深入地探索LDCD的复杂性并推动这一极具前景领域的药物发现奠定坚实基础。