Investigating the potential of GalR2 as a drug target for neuropathic pain

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Kirsty Rich , Samrina Rehman , Jeff Jerman , Graeme Wilkinson
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引用次数: 1

Abstract

Neuropathic pain is a chronic and debilitating condition characterised by episodes of hyperalgesia and allodynia. It occurs following nerve damage from disease, inflammation or injury and currently impacts up to 17% of the UK population. Existing therapies lack efficacy and have deleterious side effects that can be severely limiting.

Galanin receptor 2 (GalR2) is a G-protein coupled receptor (GPCR) implicated in the control and processing of painful stimuli. Within the nervous system it is expressed in key tissues involved in these actions such as dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. Stimulation of GalR2 is widely reported to have a role in the attenuation of inflammatory and neuropathic pain. Several studies have indicated GalR2 as a possible drug target, highlighting the potential of specific GalR2 agonists to both provide efficacy and to address the side-effect profiles of current pain therapies in clinical use.

A strong biological target for drug discovery will be well validated with regards to its role in the relevant disease pathology. Ideally there will be good translational models, sensitive probes, selective and appropriate molecular tools, translational biomarkers, a clearly defined patient population and strong opportunities for commercialisation. Before GalR2 can be considered as a drug target suitable for investment, key questions need to be asked regarding its expression profile, receptor signalling and ligand interactions. This article aims to critically review the available literature and determine the current strength of hypothesis of GalR2 as a target for the treatment of neuropathic pain.

Abstract Image

研究GalR2作为神经性疼痛药物靶点的潜力
神经性疼痛是一种慢性衰弱性疾病,其特征是出现痛觉过敏和异常性疼痛。它发生在疾病、炎症或损伤引起的神经损伤之后,目前影响了高达17%的英国人口。现有的治疗方法缺乏疗效,并且具有严重限制的有害副作用。甘丙肽受体2(GalR2)是一种G蛋白偶联受体(GPCR),与疼痛刺激的控制和处理有关。在神经系统中,它在参与这些活动的关键组织中表达,如背根神经节(DRG)和脊髓背角。GalR2的刺激被广泛报道在减轻炎症和神经性疼痛中具有作用。几项研究表明GalR2是一种可能的药物靶点,强调了特定GalR2激动剂在提供疗效和解决当前临床使用的疼痛疗法的副作用方面的潜力。药物发现的强大生物靶点将在相关疾病病理学中的作用方面得到很好的验证。理想情况下,将有良好的翻译模型、敏感的探针、选择性和适当的分子工具、翻译生物标志物、明确定义的患者群体和强大的商业化机会。在将GalR2视为适合投资的药物靶点之前,需要就其表达谱、受体信号传导和配体相互作用提出关键问题。本文旨在批判性地回顾现有文献,并确定GalR2作为神经性疼痛治疗靶点的假说的当前强度。
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
Neuropeptides
Neuropeptides 医学-内分泌学与代谢
CiteScore
5.40
自引率
6.90%
发文量
55
审稿时长
>12 weeks
期刊介绍: The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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