Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy.
Curr Drug Metab. 2017;18(12):1147-1158. doi: 10.2174/1389200218666170925125940.
Lysosomotropic molecules are taken up into lysosomes in vitro and in vivo. Many drugs approved for clinical medicine are lysosomotropic agents, characterized by promoting particular effects including cytoplasmic vacuolization, increase in number and size of lysosomes, inhibition of their enzymes and accumulation of undegraded material, leading mainly to phospholipidosis. Despite lysosomotropism has been extensively described and studied, the pathophysiological significance of this process is still not well understood. Objetive: In this review, we focus on what is known about the effects of lysosomotropic drugs on specific lysosomal functions and their similarities with the phenotypic features of lysosomal storage disorders (LSDs).
Some effects of lysosomotropic drugs are very similar to pathologic features of human genetic diseases affecting lysosomal function, and therefore these drugs can be used as tools to understand the mechanisms underlying such patho-pathways as well as to create pharmacologically-induced models of LSDs.
溶酶体靶向分子在体外和体内被摄取到溶酶体中。许多已被批准用于临床医学的药物都是溶酶体靶向剂，其特征是促进包括细胞质空泡化、溶酶体数量和大小增加、溶酶体酶抑制和未降解物质积累在内的特定效应，主要导致磷脂沉积病。尽管溶酶体靶向性已被广泛描述和研究，但该过程的病理生理学意义仍未得到很好的理解。目的：在这篇综述中，我们重点介绍了溶酶体靶向药物对特定溶酶体功能的影响及其与溶酶体贮积症（LSDs）表型特征的相似之处。结论：一些溶酶体靶向药物的作用与影响溶酶体功能的人类遗传疾病的病理特征非常相似，因此这些药物可用作工具来了解这些病理途径的机制，并创建 LSDs 的药理学诱导模型。
