An integrin approach to axon regeneration

Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites. Regeneration of sensory axons in the spinal cord can be achieved by expression of tenascin-binding alpha 9-integrin together with the integrin activator kindlin-1. This works because integrins are transported into sensory axons. Transport of integrins into retinal ganglion cell axons is seen in the retina, but may become more restricted in the optic nerve, with a subset of axons containing expressed integrins. Transduction of ganglion cells with alpha 9-integrin and kindlin-1 should promote regeneration of this subset of axons, but attention to transport may be required for regeneration of the remaining axons.