Axonal injury mediated by neuronal p75NTR/TRAF6/JNK pathway contributes to cognitive impairment after repetitive mTBI

In this study, we showed that after rmTBI, the activation of neuronal p75NTR signaling contributes to abnormal axonal morphology and impaired axonal transport, which further leads to cognitive dysfunction in mice. By neuron-specific knockdown of p75NTR or treatment with p75NTR inhibitor LM11A-31, we observed better recovery of axonal integrity and cognitive function after brain trauma. Further analysis revealed that p75NTR relies on its adaptor protein TRAF6 to activate downstream signaling via TAK1 and JNK. Overall, our results provide novel insight into the role of neuronal p75NTR in axonal injury and suggest that p75NTR may be a promising target for cognitive function recovery after rmTBI.PMID:38029807 | DOI:10.1016/j.expneurol.2023.114618

Source: Experimental Neurology - November 29, 2023 Category: Neurology Authors: Gang Liu Meijun He Chaoran Wu Pin Lv Hao Sun Heng Wang Xiaoyan Xin Hong Liao Source Type: research