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Targeting Two-Pore Channels: Current Progress and Future Challenges
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DOI：10.1016/j.tips.2020.06.002.png)
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Abstract
En 中文
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.
Keywords:
DINUCLEOTIDE PHOSPHATE NAADP
RESPIRATORY SYNDROME-CORONAVIRUS
HOST-CELL ENTRY
CA2+ SIGNALS
REGULATES AUTOPHAGY
MOBILIZES CALCIUM
PANCREATIC ACINAR
ION CHANNELS
TPCS
DIFFERENTIATION
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