Eph receptor A4 regulates motor neuron ferroptosis in spinal cord ischemia/reperfusion injury in rats

This study investigates the role of EphA4 signaling in ferroptosis following spinal cord ischemia/reperfusion injury (SCIRI) in rats. SCIRI can lead to significant neurological dysfunction and motor neuron death. The researchers found that EphA4 expression increases after SCIRI, worsening ferroptosis-related indicators and motor nerve function. Inhibiting EphA4 largely rescued the detrimental effects of SCIRI. The study also identified that EphA4 interacts with proteins such as Beclin1 and Erk1/2, promoting Beclin1-XCT complex formation and activating the Erk1/2/c-Myc/transferrin receptor 1 axis. The conclusion is that EphA4 participates in regulating ferroptosis of spinal motor neurons in SCIRI by promoting the Beclin1-XCT complex and activating the Erk1/2/c-Myc/transferrin receptor 1 axis. This suggests EphA4 as a potential therapeutic target for SCIRI.

• 1
  Spinal cord ischemia/reperfusion injury increased EphA4 expression in the neurons of anterior horn and markedly worsened ferroptosis-related indicators.
• 2
  Inhibition of EphA4 largely rescued these effects, while administration of the ferroptosis inducer Erastin counteracted the beneficial effects conferred by treatment with the EphA4 inhibitor.
• 3
  Inhibition of EphA4 expression reduced binding to Beclin1, markedly reduced p-Beclin1, and reduced Beclin1-XCT complex formation; it also reduced binding to p-Erk1/2 and markedly decreased the expression of c-Myc, transferrin receptor 1, and p-Erk1/2.