LOTUS, a potent blocker of Nogo receptor-1 causing inhibition of axonal growth.

Abstract

Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult central nervous system (CNS). Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and B lymphocyte stimulator (BLyS), are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 (NgR1), leading to inhibition of axonal growth. Here, we demonstrate that lateral olfactory tract usher substance (LOTUS) binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 ligands. LOTUS allows neurons to overcome NgR1-mediated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic approaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.