Trends in Neurosciences
Volume 44, Issue 9, September 2021, Pages 687-688
Journal home page for Trends in Neurosciences

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TRPC5 and the path towards analgesic drug development

https://doi.org/10.1016/j.tins.2021.06.010Get rights and content

A recent study by Sadler et al. highlights transient receptor potential canonical 5 (TRPC5) as a potential target for treating pain conditions. This article discusses their findings in the context of analgesic drug development, an urgent pursuit required to combat the opioid crisis and help millions of people with chronic pain.

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Acknowledgements

F.D. has received funding through an MRC New Investigator Research Grant (MR/P010814/1) and a Medical Research Foundation Prize (MRF-160-0015-ELP-DENK-C0844). She thanks Dr David Andersson for his insightful comments on this manuscript.

Declaration of interests

F.D. is on the Scientific Advisory Board of the Swedish pharmaceutical company Cellectricon.

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    Activation of TRPC5 channels leads to cell membrane depolarization and intracellular Ca2+ concentration increase. TRPC5 channel is mainly expressed in brain tissue, and also distributes to a certain extent in liver, kidney and other organs, mediating a variety of physiological processes, and is related to the generation of fear, anxiety, depression and other emotions as well as progressive kidney disease (Fig. 13b) [75–78]. TRPC5 ion channels are closely related to the pathogenesis of familial focal segmental glomerulosclerosis (FSGS).

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    Based upon their sequence homology, TRPC are divided into two classes: TRPC1/4/5 and TRPC3/6/7,3 whereas TRPC2 is a pseudogene in humans.4 Recent studies have demonstrated that TRPC channels are important regulators in pathological processes, including focal segmental sclerosis (FSGS),5–9 cardiac plasticity,10 nociception,11 psoriasis,12,13 depression,14,15 neuronal development16–18 and tumor metastasis.19,20 Recent studies have focused on TRPC5 regulation of proteinuric kidney diseases.

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