从2022年诺贝尔奖重新审视NaV1.7在疼痛中的作用

Revisiting the Role of NaV1.7 in Pain From 2022 Nobel Prize in Physiology or Medicine

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 Paabo),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Na1.7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,Na1.7与疼痛感知密切相关。本文从帕博团队Na_(v)1.7的相关研究工作出发,进一步对Na1.7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Na_(v)1.7蛋白突变位点,以及靶向Na1.7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 Paabo 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 Na1.7 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 Na1.7 is closely related to pain perception. In this review, drawing from the work of Paabo, we give a brief introduction to the expression pattern and electrophysiological properties of Na_(v)1.7, the mutation sites in Na_(v)1.7 associated with multiple pain disorders, and the drug development targeting Na_(v)1.7, including natural toxins, small molecule inhibitors and monoclonal antibodies.