TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2024-11-01 Epub Date: 2024-11-18 DOI:10.1080/14728222.2024.2430520
Klaus Groschner
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引用次数: 0

Abstract

Introduction: Intensive and detailed investigations of the molecular function and cellular role of mammalian transient receptor potential canonical (TRPC) channels started back in the early 90th of the past century. Initial TRPC research was fueled by high hopes to resolve fundamental questions of cellular Ca2+ signaling. To date, we have learned important lessons in TRPC channel biology and biophysics, while little progress has been made in terms of therapeutic concepts.

Areas covered: This is a critical account of recent progress in building a solid mechanistic basis for therapeutic interventions utilizing TRPC3 as a target. I focus on hurdles and key issues to be resolved, thereby drafting a list of essential scientific 'to-dos' on the way toward drugging of TRPC3.

Expert opinion: Recent advances in the molecular physiology of TRPC3 include unveiling its lipid sensing machinery and the channels´ ability to serve spatiotemporally diverse Ca2+ signaling in a cell type- and context-dependent manner. The ongoing development of technology for high-precision manipulation of the channel opens up a view on novel therapeutic strategies. It is now to unravel the complex role of TRPC3 in human physiopathology, to pinpoint the channels´ therapeutic relevance, and to further refine technologies for targeted interventions.

TRPC3:当前的机理认识如何为靶向治疗提供依据。
导言:对哺乳动物瞬时受体电位通道(TRPC)的分子功能和细胞作用的深入细致研究始于上世纪 90 年代初。人们对解决细胞 Ca2+ 信号转导的基本问题寄予厚望,从而推动了最初的 TRPC 研究。迄今为止,我们已在 TRPC 通道生物学和生物物理学方面汲取了重要的经验教训,但在治疗概念方面却进展甚微:这是在利用 TRPC3 作为靶点为治疗干预建立坚实的机理基础方面取得的最新进展的重要论述。我将重点放在有待解决的障碍和关键问题上,从而起草了一份通往 TRPC3 药物治疗之路的基本科学 "待办事项 "清单:TRPC3 分子生理学的最新进展包括揭示了其脂质传感机制,以及该通道以细胞类型和环境依赖性方式服务于时空多样性 Ca2+ 信号转导的能力。高精度操纵通道技术的不断发展为新型治疗策略开辟了前景。现在的任务是揭示 TRPC3 在人类生理病理学中的复杂作用,确定该通道的治疗相关性,并进一步完善靶向干预技术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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