Integrin manipulation to improve regeneration

After central nervous system (CNS) insults, neurons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Two recent studies show that activating integrin signaling in dorsal root ganglion (DRG) neurons renders them able to overcome inhibitory signals, and could possibly lead to new strategies to improve neuronal regeneration. Axonal growth cones interact with the extracellular matrix (ECM), by cell-surface receptors such as members of the integrin family.

• 1
  Addition of CSPGs to dorsal root ganglion (DRG) cultures resulted in a reduction of activated integrins and growth inhibition. By adding manganese to the cultures, both FAK phosphorylation and growth response was restored, indicating that integrin activation is sufficient to override the inhibitory effects of CSPGs.
• 2
  Overexpression of kindlin-1 in DRG neurons lead to an increase in integrin activation and an increase in phosphorylation of FAK in axons.
• 3
  Injection of virus vectors carrying kindlin-1 constructs into the DRG lead to ingrowth of axons into the dorsal horn and dorsal column of the spinal cord and led to functional recovery of thermal but not pressure sensation in the forepaw.