2022年诺贝尔生理学或医学奖获得者———瑞典科学家斯万特·帕博(Svante P??bo),在他2020年发表的一项研究中揭示,与现代人的蛋白质序列相比,已灭绝人种———尼安德特人的电压门控钠通道NaV1.7蛋白存在三个突变位点,导致通道活性发生显著改变。既往大量的遗传学证据表明,NaV1.7与疼痛感知密切相关。本文从帕博团队NaV1.7的相关研究工作出发,进一步对NaV1.7的表达模式、电生理学特性、已鉴定的与多种疼痛疾病相关的NaV1.7蛋白突变位点,以及靶向NaV1.7的镇痛药物研发(天然毒素、小分子抑制剂和单克隆抗体)进行简要综述。

In 2022, the Swedish scientist Svante P??bo was awarded the Nobel Prize in Physiology or Medicine, in whose study published in 2020, 3 mutations were discovered to have existed in the sequence of the voltage-gated sodium channel NaV1.7 in the extinct Neanderthals compared to that in modern humans, which led to remarkable changes of the channel activity. In previous studies, large amounts of genetic evidence have indicated that NaV1.7 is closely related to pain perception. In this review, drawing from the work of P??bo, we give a brief introduction to the expression pattern and electrophysiological properties of NaV1.7, the mutation sites in NaV1.7 associated with multiple pain disorders, and the drug development targeting NaV1.7, including natural toxins, small molecule inhibitors and monoclonal antibodies.