将 TRPC5 受体作为治疗疼痛和代谢疾病的药理靶点。

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Pragyanshu Khare , Jagdish Chand , Alexandra Ptakova , Renato Liguori , Fulvia Ferrazzi , Mahendra Bishnoi , Viktorie Vlachova , Katharina Zimmermann
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引用次数: 0

摘要

瞬时受体电位通道(TRPC)是 TRP 通道家族中一组高度同源的非选择性阳离子通道。它们能够形成具有不同程度钙(Ca2+)通透性和信号特性的同源异构体。TRPC5 是其中对冷敏感的通道,它同样能促进细胞外 Ca2+ 流入细胞,从而调节神经元去极化并整合各种细胞内信号通路。最近利用低温电子显微镜进行的研究揭示了它的结构,并清楚地了解了下游信号传导和蛋白质间相互作用的位点。利用整体和条件性缺陷小鼠进行的研究发现,TRPC5 参与了代谢性疾病、能量平衡、热感觉以及骨关节炎、类风湿性关节炎和炎症性疼痛等疾病的治疗,包括阿片类药物诱导的痛觉减退和蛀牙及牙髓炎后的痛觉减退。本综述介绍了我们对 TRPC5 作用的最新理解进展,重点关注代谢性疾病和疼痛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The TRPC5 receptor as pharmacological target for pain and metabolic disease
The transient receptor potential canonical (TRPC) channels are a group of highly homologous nonselective cation channels from the larger TRP channel family. They have the ability to form homo- and heteromers with varying degrees of calcium (Ca2+) permeability and signalling properties. TRPC5 is the one cold-sensitive among them and likewise facilitates the influx of extracellular Ca2+ into cells to modulate neuronal depolarization and integrate various intracellular signalling pathways. Recent research with cryo-electron microscopy revealed its structure, along with clear insight into downstream signalling and protein-protein interaction sites. Investigations using global and conditional deficient mice revealed the involvement of TRPC5 in metabolic diseases, energy balance, thermosensation and conditions such as osteoarthritis, rheumatoid arthritis, and inflammatory pain including opioid-induced hyperalgesia and hyperalgesia following tooth decay and pulpitis. This review provides an update on recent advances in our understanding of the role of TRPC5 with focus on metabolic diseases and pain.
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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
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