LOTUS as an endogenous protein converting the adult central nervous system environment from nonpermissive to permissive for axonal regrowth after brain injury.

Central nervous system (CNS) injury, such as spinal cord injury (SCI), results in severe sensory and motor deficits due to the poor regenerative capacity of the adult CNS primarily caused by a damaged CNS environment containing a large amount of axonal growth inhibitors, such as Nogo receptor-1 (NgR1), which inhibits axonal regrowth strongly after SCI, and its five ligands. Lateral olfactory tract usher substance (LOTUS), identified in the developing brain, completely antagonizes NgR1 function, promoting neuronal regeneration and functional recovery after SCI. Therefore, we hypothesized that LOTUS might be a useful natural agent for the clinical treatment of SCI in order to increase functional recovery by converting the CNS environment from nonpermissive to permissive for neuronal regeneration. Currently, we are attempting to administer LOTUS after SCI by protein injection or gene transfection. In this report, I discuss the probability of clinical application of LOTUS for future therapy of brain injury.