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钠离子通道 1.7 作为疼痛的药物基因组靶点:迈向精准医学。

Na1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine.

机构信息

Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, and Purdue Institute for Integrative Neuroscience, West Lafayette, IN 47907, USA.

Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.

出版信息

Trends Pharmacol Sci. 2018 Mar;39(3):258-275. doi: 10.1016/j.tips.2017.11.010. Epub 2018 Jan 20.

Abstract

Chronic pain is a global unmet medical need. Most existing treatments are only partially effective or have side effects that limit their use. Rapid progress in elucidating the contribution of specific genes, including those that encode peripheral voltage-gated sodium channels, to the pathobiology of chronic pain suggests that it may be possible to advance pain pharmacotherapy. Focusing on voltage-gated sodium channel Na1.7 as an example, this article reviews recent progress in developing patient-specific induced pluripotent stem cells (iPSCs) and their differentiation into sensory neurons, together with advances in structural modeling, that have provided a basis for first-in-human translational studies. These new approaches will hopefully transform the treatment of pain from trial-and-error toward genomically guided, precision pharmacotherapy.

摘要

慢性疼痛是全球性的未满足医学需求。大多数现有治疗方法仅部分有效,或具有限制其使用的副作用。阐明特定基因(包括编码外周电压门控钠离子通道的基因)对慢性疼痛发病机制的贡献方面的快速进展表明,推进疼痛药物治疗是可能的。本文以电压门控钠离子通道 Na1.7 为例,综述了开发患者特异性诱导多能干细胞(iPSC)及其向感觉神经元分化的最新进展,以及结构建模方面的进展,这些进展为首次人体转化研究提供了基础。这些新方法有望将疼痛治疗从试错法转变为基于基因组的精准药物治疗。

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