Extracellular phosphorylation is a novel target for regenerative medicine against spinal cord injury

Abstract

The mammalian adult central nervous system (CNS) can be hardly regenerated after traumatic damage, and therapeutic methods for promoting CNS regeneration are strongly desired. Nogo‐A is a membrane protein present in CNS myelin. Models of spinal cord injury (SCI) in rats and macaque monkeys demonstrate that treatment with neutralising antibodies against Nogo‐A results in the formation of new functional connections in the spinal cord. A Phase I clinical trial applying anti‐Nogo‐A antibody to subjects with acute SCI has been successfully conducted. We reported that phosphorylation of extracellular domains of Nogo‐A receptors inhibits ligand binding, enabling neurite outgrowth even in the presence of Nogo‐A, in vitro (Takei, Science signaling, 2009). Here, we examined the effects of the extracellular kinase treatment on the recovery from SCI with rat model. Marked behavioural improvement was observed in the lesioned animals after the extracellular kinase treatment. These results provide a launching point for developing methods to stimulate neuronal regeneration in the adult mammalian CNS. Thus, our results provide evidence that artificial modification of extracellular domains of membrane receptors can be novel targets for drug discovery.