Lysosomal Ion Channels: What Are They Good For and Are They Druggable Targets?

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Erika Riederer, Chunlei Cang, Dejian Ren
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引用次数: 5

Abstract

Lysosomes play fundamental roles in material digestion, cellular clearance, recycling, exocytosis, wound repair, Ca2+ signaling, nutrient signaling, and gene expression regulation. The organelle also serves as a hub for important signaling networks involving the mTOR and AKT kinases. Electrophysiological recording and molecular and structural studies in the past decade have uncovered several unique lysosomal ion channels and transporters, including TPCs, TMEM175, TRPMLs, CLN7, and CLC-7. They underlie the organelle's permeability to major ions, including K+, Na+, H+, Ca2+, and Cl-. The channels are regulated by numerous cellular factors, ranging from H+ in the lumen and voltage across the lysosomal membrane to ATP in the cytosol to growth factors outside the cell. Genetic variations in the channel/transporter genes are associated with diseases that include lysosomal storage diseases and neurodegenerative diseases. Recent studies with human genetics and channel activators suggest that lysosomal channels may be attractive targets for the development of therapeutics for the prevention of and intervention in human diseases.

溶酶体离子通道:它们有什么好处,它们是可药物靶点吗?
溶酶体在物质消化、细胞清除、循环、胞外分泌、伤口修复、Ca2+信号传导、营养信号传导和基因表达调控等方面发挥着重要作用。细胞器也作为重要信号网络的枢纽,包括mTOR和AKT激酶。在过去的十年中,电生理记录和分子和结构研究发现了几种独特的溶酶体离子通道和转运体,包括TPCs, TMEM175, trpml, CLN7和CLC-7。它们是细胞器对主要离子的渗透性的基础,包括K+, Na+, H+, Ca2+和Cl-。这些通道受到许多细胞因子的调节,从管腔中的H+和溶酶体膜上的电压到细胞质中的ATP再到细胞外的生长因子。通道/转运基因的遗传变异与溶酶体贮积病和神经退行性疾病等疾病有关。最近对人类遗传学和通道激活剂的研究表明,溶酶体通道可能是开发预防和干预人类疾病的治疗方法的有吸引力的靶点。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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