Abstract :Abstract
After spinal cord injury (SCI), primates, such as humans, hardly ever recover the affected motor function. The primary cause of limited neuronal regeneration in the central nervous system is the interaction between axon growth inhibitors such as Nogo protein and Nogo receptor-1 (NgR1), a common receptor of these inhibitors,. We have previously shown that lateral olfactory tract usher substance (LOTUS) identified in the developing brain contributes to axon tract formation by antagonizing Nogo-NgR1 mediated signaling. Furthermore we also found that the binding of LOTUS to NgR1 blocks thisNgR1-mediated axon growth inhibition. We therefore hypothesized that LOTUS may promote neuronal regeneration by antagonizing NgR1. To address this issue, we examined functional and histological recovery after SCI in wild type, lotus- deficient (LOTUS- KO) and LOTUS over expressing transgenic (LOTUS- TG) mice. We found that LOTUS- KO mice lost spontaneous functional recovery after SCI, whereas LOTUS-TG mice increased functional recovery when respectively compared with wild type mice. These findings suggest that LOTUS promotes neuronal regeneration after SCI by blockade of NgR1 function and is useful as a natural agent for clinical treatment of SCI. We are currently attempting to administer LOTUS after SCI by protein injection, gene transfection or transplantation of LOTUS over expressing neuronal stem cells.