美国哈佛医学院Isaac M. Chiu团队发现，炭疽毒素可调节疼痛信号。相关论文于2021年12月20日在线发表在《自然—神经科学》杂志上。
研究人员发现，背根神经节（DRG）的感觉神经元富含ANTXR2，即炭疽毒素的高亲和力受体。炭疽毒素由保护性抗原（PA）组成，它与ANTXR2结合，还有蛋白质货物水肿因子（EF）和致死因子（LF）。水肿毒素（ET（PA+EF））的鞘内给药以DRG神经元为靶标，并诱发小鼠的镇痛。ET抑制了机械和热感觉，以及由福尔马林、卡拉胶或神经损伤引起的疼痛。镇痛作用取决于Nav1.8+或Advillin+神经元表达的ANTXR2。ET调节了小鼠感觉和人类诱导多能干细胞衍生的感觉神经元中的蛋白激酶A信号，并削弱了脊髓神经传递。
研究人员进一步设计了炭疽毒素，将包括肉毒杆菌毒素在内的外源性蛋白货物引入DRG神经元，以抑制疼痛。这项研究强调了细菌毒素和痛觉感受器之间的相互作用，这可能导致新型疼痛治疗方法的开发。
据悉，细菌产物可以作用于神经元来改变信号传递和功能。
附：英文原文
Title: Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons
Author: Yang, Nicole J., Isensee, Jrg, Neel, Dylan V., Quadros, Andreza U., Zhang, Han-Xiong Bear, Lauzadis, Justas, Liu, Sai Man, Shiers, Stephanie, Belu, Andreea, Palan, Shilpa, Marlin, Sandra, Maignel, Jacquie, Kennedy-Curran, Angela, Tong, Victoria S., Moayeri, Mahtab, Rderer, Pascal, Nitzsche, Anja, Lu, Mike, Pentelute, Bradley L., Brstle, Oliver, Tripathi, Vineeta, Foster, Keith A., Price, Theodore J., Collier, R. John, Leppla, Stephen H., Puopolo, Michelino, Bean, Bruce P., Cunha, Thiago M., Hucho, Tim, Chiu, Isaac M.
Issue&Volume: 2021-12-20
Abstract: Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF). Intrathecal administration of edema toxin (ET (PA+EF)) targeted DRG neurons and induced analgesia in mice. ET inhibited mechanical and thermal sensation, and pain caused by formalin, carrageenan or nerve injury. Analgesia depended on ANTXR2 expressed by Nav1.8+ or Advillin+ neurons. ET modulated protein kinase A signaling in mouse sensory and human induced pluripotent stem cell-derived sensory neurons, and attenuated spinal cord neurotransmission. We further engineered anthrax toxins to introduce exogenous protein cargoes, including botulinum toxin, into DRG neurons to silence pain. Our study highlights interactions between a bacterial toxin and nociceptors, which may lead to the development of new pain therapeutics.
DOI: 10.1038/s41593-021-00973-8
Source: https://www.nature.com/articles/s41593-021-00973-8
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
