Iron Metabolism and Ferroptosis in Peripheral Nerve Injury

Peripheral nerve injury (PNI) can lead to sensory and motor dysfunction. Exploration of PNI mechanisms is required due to high disability rates. Ferroptosis, a novel form of cell death, is iron-dependent and involves multiple cellular metabolic pathways. Inhibition of ferroptosis can promote nerve repair and recovery. Iron metabolism needs strict regulation in the human body. Abnormal iron metabolism is closely associated with the defective repair process after a damage to the nervous system. Ferroptosis, first defined in 2012, is a new form of regulated cell death (RCD), which is dependent on iron ions. After PNI, a microenvironment is established with increased iron ions and ROS levels, contributing to ferroptosis. This causes further damage to Schwann cells and axons, exacerbating nerve damage, neuropathic pain, or neuroinflammation.

• 1
  Ferroptosis involves iron overload, lipid peroxidation, ROS generation, and mitochondrial changes, contributing to nerve damage in PNI.
• 2
  The system xc--GSH-GPX4 axis plays a key role in ferroptosis, and regulating this axis after PNI could potentially promote nerve cell regeneration and functional recovery.
• 3
  Inhibiting ferroptosis can alleviate tissue damage and promote functional recovery after PNI, suggesting its essential role in PNI.