Mechanisms of Axon Elongation Following CNS Injury: What Is Happening at the Axon Tip?

After a CNS injury, axons often fail to regenerate, limiting functional recovery. This review examines the cytoskeletal underpinnings of axon growth, focusing on the elongating axon tip, to gain insights into how CNS axons respond to injury. The growth cone, rich in actin, microtubule, and neurofilament proteins, is crucial for tip-mediated axon extension during development. The review focuses on how cytoskeletal dynamics at the axon tip contribute to regenerative axon extension after CNS injury. The review also addresses how growth-inhibitory signals affect the actin filament cytoskeleton, considering actin filament organization and distribution, which goes beyond just the levels of actin filaments.

• 1
  Axon resealing after injury is an active, calcium-driven process, which facilitates cytoskeletal depolymerization and repolymerization needed to form a growth cone.
• 2
  The actin filament cytoskeleton and growth cones are not always required for axon extension, as the requirement for them depends on neuron-intrinsic and extrinsic factors.
• 3
  Regeneration-inhibiting signals decrease growth cone complexity, and impact the organization of actin filaments, setting the tip of the axon in a contractile state, which is functionally opposite to that required to promote extension and guidance.