Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission
oleh: Michele Yeo, Yong Chen, Changyu Jiang, Gang Chen, Kaiyuan Wang, Sharat Chandra, Andrey Bortsov, Maria Lioudyno, Qian Zeng, Peng Wang, Zilong Wang, Jorge Busciglio, Ru-Rong Ji, Wolfgang Liedtke
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2021-10-01 |
Deskripsi
Lack of expression and function of chloride ion-extruding transporter KCC2 in central neurons, a consequence of various forms of neural injury, is strongly suggested to contribute to chronic pain. Here the authors identify from a screen of cancer drugs a kinase-inhibitor, kenpaullone, as an enhancer of Kcc2/KCC2 gene expression and show that it (i) alleviates pain like behaviour in animal models, (ii) repairs neural-circuit disrupting elevated chloride in pain relay neurons in the dorsal spinal cord.