Modulating lysosomal pH: a molecular and nanoscale materials design perspective.
Modulating lysosomal pH: a molecular and nanoscale materials design perspective.
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DOI：
10.36069/jols/20201204
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Grinstaff MW
中科院分区：
文献类型：
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作者：
Zeng J;Shirihai OS;Grinstaff MW
溶酶体是一种膜结合细胞器，在细胞内吞、吞噬和自噬等过程中起着重要作用。溶酶体通过产生pH为4.5 - 5.0的高酸性环境和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，特别是其酸化，是神经退行性疾病、癌症、代谢紊乱和传染病发病的驱动力。因此，溶酶体pH值是治疗干预的一个有吸引力和可靶向的位点。目前，缺乏可用于特异性调节溶酶体酸化的策略或材料。本文综述了溶酶体pH与各种疾病的关系，并讨论了溶酶体pH调节的设计策略和分子或纳米级药物，最终目标是开发新的治疗方案。
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.