Cerebral dopamine neurotrophic factor for spinal cord injury: Targeting JNK1 to relieve neuroinflammation and improve neural repair

Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis, necrosis, and pro-inflammatory microenvironment after spinal cord injury. The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species. Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury. However, the molecular mechanism remains unclear. In this study, we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia. Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines. Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery. These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.