Axonal Regeneration after Spinal Cord Injury: Molecular Mechanisms, Regulatory Pathways, and Novel Strategies

The main challenge of axonal regeneration after traumatic injuries of the spinal cord consists of overcoming the activation of inhibitory pathways. Understanding the molecular mechanisms affecting regrowth (like the PKA/AMP, PI3K/Akt/mTOR pathways) and guidance cues (like neurotrophins) is thus essential. The use of gene therapy, tissue engineering, and small therapeutic molecules show a promising track to overcome inhibitory mechanisms to axonal regrowth.

• 1
  Inhibiting PTEN promotes axonal regeneration and elongation, emphasizing the significance of PTEN/Akt/mTOR signaling pathway activation, particularly in cerebral cortical neurons.
• 2
  Myelin-associated inhibitors (MAIs), like Nogo-A, MAG, and OMgp, along with other pathways such as Rho GTPases, cAMP signaling, PI3K/Akt/mTOR, and JAK/STAT3, are involved in complex mechanisms and pathways inhibiting axonal regeneration after SCI.
• 3
  Emerging treatment strategies offer promising approaches for promoting neural regeneration by enhancing cAMP signaling, inhibiting PTEN, and modulating the JAK/STAT3 pathway.