THE EFFECT OF RECEPTOR PROTEIN TYROSINE PHOSPHATASE SIGMA (RPTP- DOLLAR G(S)) ON NEURAL AXON REGENERATION AND SYNAPSE MODIFICATION

摘要

A novel effect of the receptor protein tyrosine phosphatase sigma (RPTP- sigma ), which regulates neural regeneration in the adult mammalian nervous system, is disclosed. It is shown herein that in adult mice lacking RPTP- sigma function,the rate of regeneration is enhanced. It is shown that axon growth from dissociated neurons in vitro is enhanced in the absence of RPTP- sigma . These findings indicate that RPTP- sigma is a critical regulator of axon outgrowth. It is also disclosed that RPTP- sigma is concentrated at neuronal synaptic connections, supporting a role for RPTP- sigma regulating synapse formation during development and synaptic modification in adults. On this basis there is provided herein a method of modulating the activity of RPTP- sigma and a use of an inhibitor of RPTP- sigma in the making of a medication for promoting neuronal axon regeneration upon nerve injury in a mammalian nervous system. Futhermore, on this basis there is provided herein a method of modulating the activity of RPTP- sigma and a use of an activator of RPTP- sigma in the making of a medication for inhibiting neuronal axon growth in a mammalian nervous system in a circumstance where abnormal sprouting contributes to a pathological state, such as a chronic pain. This inhibitor or activator is selected from the group consisting of an antisense nucleotide, a ribozyme, a peptide, a monoclonal antibody and an antagonist. There is also provided an in vitro assay for the identification of modulators of RPTP- sigma activity.