Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment

Following injury to the central nervous system (CNS), scar tissue forms, which inhibits the regeneration of nerve fibers in mammals but not in zebrafish. This study identifies a group of proteins called small leucine-rich proteoglycans (SLRPs) as a key factor contributing to this difference, finding them enriched in mammalian scars but not in regenerating zebrafish. The presence of SLRPs modifies the physical properties of the scar tissue, making it less conducive to nerve fiber growth. Thus, targeting these proteins could potentially promote CNS regeneration after injury.

• 1
  SLRPs, including chondroadherin, fibromodulin, lumican, and prolargin, are enriched in rodent and human CNS lesions but not in zebrafish.
• 2
  Increasing SLRP levels in zebrafish injury sites inhibits axon regeneration and functional recovery, demonstrating their inhibitory role.
• 3
  SLRPs modify the structural and mechanical properties of the lesion environment, making it adverse to axon growth.