Ubiquitin ligase Triad1 promotes neurite outgrowth by inhibiting MDM2-mediated ubiquitination of the neuroprotective factor pleiotrophin

Spinal cord injury (SCI) often results in nerve structure damage and nerve dysfunction. After SCI, neurons have limited neurite growth ability, hindering nerve function restoration. This study investigates the role of Triad1, an E3 ubiquitin ligase, in promoting neurite outgrowth after SCI by inhibiting MDM2-mediated ubiquitination of pleiotrophin (PTN). The research uses a SCI rat model and cultured rat astrocytes and neurons to systematically examine the effects of Triad1, MDM2, and PTN on astrocyte function, neurite outgrowth, and functional recovery after SCI.

• 1
  Triad1 overexpression promoted PTN protein levels, NGF expression, BDNF expression, astrocyte and neuronal viability, and neurite outgrowth but suppressed astrocyte apoptosis.
• 2
  MDM2 overexpression downregulated PTN protein levels, NGF expression and BDNF expression in astrocytes, and inhibited neurite outgrowth of neurons; MDM2 facilitated PTN ubiquitination, which was reversed by Triad1.
• 3
  Triad1 improved the motor function and histomorphological injury of SCI rats, suggesting its therapeutic potential.