Targeting Two-Pore Channels: Current Progress and Future Challenges

被引：36

作者：

Jin, Xuhui ^{[1
]}

Zhang, Yuxuan ^{[1
]}

Alharbi, Abeer ^{[1
]}

Hanbashi, Ali ^{[1
]}

Alhoshani, Ali ^{[2
]}

Parrington, John ^{[1
]}

机构：

[1] Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England

[2] King Saud Univ, Dept Pharmacol & Toxicol, Coll Pharm, POB 2457, Riyadh 11454, Saudi Arabia

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2020年 / 41卷 / 08期

关键词：

DINUCLEOTIDE PHOSPHATE NAADP; RESPIRATORY SYNDROME-CORONAVIRUS; HOST-CELL ENTRY; CA2+ SIGNALS; REGULATES AUTOPHAGY; MOBILIZES CALCIUM; PANCREATIC ACINAR; ION CHANNELS; TPCS; DIFFERENTIATION;

D O I：

10.1016/j.tips.2020.06.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Two-pore channels (TPCs) are cation-permeable channels located on endolysosomal membranes and important mediators of intracellular Ca2+ signal- ling. TPCs are involved in various pathophysiological processes, including cell growth and development, metabolism, and cancer progression. Most studies of TPCs have used TPC-/- cell or whole-animal models, or Ned-19, an indirect inhibitor. The TPC activation mechanism remains controversial, which has made it diff i cult to develop selective modulators. Recent studies of TPC structure and their interactomes are aiding the development of direct pharmacological modulators. This process is still in its infancy, but will facilitate future research and TPC targeting for therapeutical purposes. Here, we review the progress of current research into TPCs, including recent insights into their structures, functional roles, mechanisms of activation, and pharmacological modulators.

引用

页码：582 / 594

页数：13

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