自然杂志 ›› 2018, Vol. 40 ›› Issue (6): 435-444.doi: 10.3969/j.issn.0253-9608.2018.06.007

• 科技进展 • 上一篇    下一篇

Nav1.7离子通道作为疼痛的药物靶标：向精准医学迈进

刘雅梅①，刘玉霜②，张精亮②，王静①，李敏①，陈付学①，杨洋②③   

  1. ①上海大学 生命科学学院，上海 200444；②普渡大学 药学院药物化学及分子药理系，西拉法叶市，印第安纳州47907，美国；③耶鲁大学 医学院神经学系/神经科学与再生研究中心，纽黑文市，康乃狄格州 06510，美国
  • 收稿日期:2018-12-21 出版日期:2018-12-25 发布日期:2018-12-21
  • 通讯作者: 研究方向：离子通道相关疾病的机制及药物靶标，对持久痛、癫痫、自闭症等神经系统疾病的精准治疗

Focusing on Nav1.7 channel: moving towards pain precision medicine

LIU Yamei①, LIU Yushuang②, ZHANG Jingliang②, WANG Jing①, LI Min①, CHEN Fuxue①,YANG Yang②③   

  1. ①School of Life Science, Shanghai University, Shanghai 200444, China; ②Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, IN 47907, USA; ③Department of Neurology and Center for Neuroscience and Regeneration Research, School of Medicine, Yale University, New Haven, CT06510, USA
  • Received:2018-12-21 Online:2018-12-25 Published:2018-12-21

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摘要：

安全有效地治疗慢性疼痛是全球性尚未解决的医疗难题，现有的治疗或是部分有效，或是因其副作用而被限制使用。对慢性疼痛病理学相关的特定基因功能研究的快速进展，例如阐明编码外周电压门控钠通道的基因功能，能够推进疼痛药物治疗的发展。以电压门控钠通道Nav1.7为例，综述了对患者细胞进行特异性诱导多能干细胞(iPSCs)操作并分化成感觉神经元，以及在结构建模方面取得的进展，展示了从基础研究到临床转化的可能性。这些新的方法将有望实现从试错治疗到基因引导的疼痛精确药物治疗的转变。

关键词: Nav1.7, 疼痛, 药物靶标

Abstract:

Chronic pain is a global unmet medical need. Most available treatments are only partially effective or have side effects that limit their utilities. Rapid progress has been made to elucidate the contributions of specific genes to the chronic pain, suggesting possibility to advance pain pharmacotherapy. Focusing on voltage-gated sodium channel Nav1.7 as an example, this article reviews recent progress in painpharmacogenomics, new development of disease models using patient-specific induced pluripotent stem cells (iPSCs) derived sensory neurons, as well as advances in structural modeling and electrophysiology recording.These new approaches will hopefully transform the treatment of pain from trial-and-error toward precision pharmacotherapy.

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