近日，以色列魏茨曼科学研究所Mike Fainzilber及其团队发现，输入蛋白α3调节周围感觉神经元的慢性疼痛通路。相关论文发表在2020年8月14日出版的《科学》杂志上。

研究人员发现，输入蛋白α3（也称为karyopherin亚基α4）可以控制小鼠周围感觉神经元的疼痛反应。输入蛋白α3基因敲除或小鼠感觉神经元特异性敲低会降低对各种有害刺激的反应，并增加对神经性疼痛的耐受性。

输入蛋白α3结合的c-Fos和输入蛋白α3缺陷的神经元会在c-Fos核输入中受损。降低感官神经元中的c-Fos或c-Jun的抑制或显性负抑制作用可减轻神经性疼痛。模拟筛选发现了模仿输入蛋白α3缺失的药物。

这些药物减轻了神经性疼痛并降低了c-Fos核定位。因此，在周围神经元中通过输入蛋白α3干扰c-Fos核输入可以促进镇痛作用。

据悉，周围感觉神经元的神经性疼痛如何调节尚不清楚。输入蛋白是核质运输的关键调节因子。

附：英文原文

Title: Importin α3 regulates chronic pain pathways in peripheral sensory neurons

Author: Letizia Marvaldi, Nicolas Panayotis, Stefanie Alber, Shachar Y. Dagan, Nataliya Okladnikov, Indrek Koppel, Agostina Di Pizio, Didi-Andreas Song, Yarden Tzur, Marco Terenzio, Ida Rishal, Dalia Gordon, Franziska Rother, Enno Hartmann, Michael Bader, Mike Fainzilber

Issue&Volume: 2020/08/14

Abstract: How is neuropathic pain regulated in peripheral sensory neurons Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control pain responsiveness in peripheral sensory neurons in mice. Importin α3 knockout or sensory neuron–specific knockdown in mice reduced responsiveness to diverse noxious stimuli and increased tolerance to neuropathic pain. Importin α3–bound c-Fos and importin α3–deficient neurons were impaired in c-Fos nuclear import. Knockdown or dominant-negative inhibition of c-Fos or c-Jun in sensory neurons reduced neuropathic pain. In silico screens identified drugs that mimic importin α3 deficiency. These drugs attenuated neuropathic pain and reduced c-Fos nuclear localization. Thus, perturbing c-Fos nuclear import by importin α3 in peripheral neurons can promote analgesia.

DOI: 10.1126/science.aaz5875

Source: https://science.sciencemag.org/content/369/6505/842