Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration

After trauma, regeneration of adult CNS axons is abortive, causing devastating neurologic deficits. Despite progress in rehabilitative care, there is no effective treatment that stimulates axonal growth following injury. Using models with different regenerative capacities, followed by gain- and loss-of-function analysis, we identified profilin 1 (Pfn1) as a coordinator of actin and microtubules (MTs), powering axonal growth and regeneration. In vivo, Pfn1 ablation limited regeneration of growth-competent axons after sciatic nerve and spinal cord injury. Adeno-associated viral (AAV) delivery of constitutively active Pfn1 to rodents promoted axonal regeneration, neuromuscular junction maturation, and functional recovery of injured sciatic nerves, and increased the ability of regenerating axons to penetrate the inhibitory spinal cord glial scar.

• 1
  Pfn1 activity increases after CL, suggesting it's important for actin dynamics in the axonal tip and for growth competence.
• 2
  Pfn1 downregulation impairs axonal growth in different neuronal types and developmental stages.
• 3
  In vivo depletion of Pfn1 curbs axonal regeneration in the peripheral and central nervous systems.