Zeng Jialiu, Shirihai Orian S, Grinstaff Mark W
Department of Biomedical Engineering, Boston University, Boston, MA 02215.
Department of Neurology, School of Medicine, Yale University, New Haven, CT 06511.
J Life Sci (Westlake Village). 2020 Dec;2(4):25-37. doi: 10.36069/jols/20201204.
Lysosomes, membrane-bound organelles, play important roles in cellular processes including endocytosis, phagocytosis, and autophagy. Lysosomes maintain cellular homeostasis by generating a highly acidic environment of pH 4.5 - 5.0 and by housing hydrolytic enzymes that degrade engulfed biomolecules. Impairment of lysosomal function, especially in its acidification, is a driving force in the pathogenesis of diseases including neurodegeneration, cancer, metabolic disorders, and infectious diseases. Therefore, lysosomal pH is an attractive and targetable site for therapeutic intervention. Currently, there is a dearth of strategies or materials available to specifically modulate lysosomal acidification. This review focuses on the key aspects of how lysosomal pH is implicated in various diseases and discusses design strategies and molecular or nanoscale agents for lysosomal pH modulation, with the ultimate goal of developing novel therapeutic solutions.
溶酶体是膜结合细胞器，在包括内吞作用、吞噬作用和自噬作用在内的细胞过程中发挥重要作用。溶酶体通过产生pH值为4.5 - 5.0的高度酸性环境以及容纳降解被吞噬生物分子的水解酶来维持细胞内稳态。溶酶体功能的损害，尤其是其酸化过程的损害，是包括神经退行性疾病、癌症、代谢紊乱和传染病在内的多种疾病发病机制中的一个驱动因素。因此，溶酶体pH值是一个有吸引力且可靶向的治疗干预位点。目前，缺乏可用于特异性调节溶酶体酸化的策略或材料。本综述重点关注溶酶体pH值与各种疾病的关联的关键方面，并讨论用于溶酶体pH值调节的设计策略以及分子或纳米级试剂，最终目标是开发新的治疗方案。
