Mechanisms of CNS myelin inhibition: Evidence for distinct and neuronal cell type specific receptor systems

摘要: Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack neuronal repair often associated with significant functional deficits, and depending on severity injury, may result in permanent paralysis distal site injury. A detailed understanding molecular mechanisms that limit injured spinal cord an important step toward development specific strategies aimed at restoring connectivity lost as a consequence While rapid progress being made defining identity CNS inhibitory constituents, comparatively little known about their receptors downstream signaling mechanisms. Emerging new evidence suggests for myelin inhibition are likely be complex, involving multiple distinct receptor systems operate redundant manner. Furthermore, relative contribution ligand-receptor system bring greatly vary among different cell types. Myelin-associated glycoprotein (MAG), example, employs inhibit neurite outgrowth cerebellar, sensory, retinal ganglion neurons vitro. Nogo-A harbors regions, which employ Nogo-66 1 (NgR1), shared ligand binding component complex Nogo-66, MAG, OMgp, participates cone collapse acutely presented inhibitors, but dispensable longitudinal substrate-bound or crude Consistent idea cell-type inhibition, types possess capacities respond differently experimental treatment vivo. We speculate differences axonal fiber reflection intrinsic ability elongate surface profiles extracellular milieu. existence type impair have implications strategies. Depending tract injured, need targeted order elicit robust long-distance growth.