Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury

Axonal organelles like the endoplasmic reticulum, mitochondria, and endosomes are crucial for axon growth and regeneration after injuries like spinal cord injury or vision loss. These organelles act as centers for organizing molecular mechanisms required for growth cone development and axon extension. This review explores how organelles such as recycling endosomes, endoplasmic reticulum, mitochondria, lysosomes, autophagosomes, and proteasomes play a central role in developmental axon growth. It further investigates how targeting these organelles can promote axon regeneration in the adult CNS after injury. The review summarizes evidence for intracellular organelles as sites of convergence for growth and regeneration-associated pathways. It discusses the roles of inter-organelle connections in axon growth and regeneration, and how targeting organelles or multi-organellar complexes could stimulate axon growth.

• 1
  The endoplasmic reticulum (ER) is crucial for lipid and protein synthesis, calcium homeostasis, and acts as a platform for signaling proteins important for growth and response to injury.
• 2
  Mitochondria are essential for developmental axon growth and regeneration, acting as molecular platforms for intracellular signaling.
• 3
  Endosomes are key sites for the localization, recycling, and degradation of growth-associated cargo, and their regulation in neurons has key implications for axon growth and regeneration.
• 4
  Autophagosomes and lysosomes/late endosomes contribute to axon growth and regeneration by regulating autophagy, intracellular signaling, and exocytosis.
• 5
  The proteasome plays an essential role in protein balance in newly growing and regenerating axons, with its activity requiring a critical level of regulation.