Research groups at Waseda University, the National Center of Neurology and Psychiatry, and Yokohama City University have shown that the regeneration of the optic nerve damaged by external force is promoted by the inhibition of phosphorylation of a protein called CRMP2.
Once damaged, the central nervous system, such as the brain and spinal cord, does not regenerate, making it difficult to treat neurological disorders.Regeneration includes neurogenesis in which new nerve cells are created, and nerve axon regeneration in which axons of once cut and damaged nerves are re-elongated.Neurogenesis in the adult brain has many unclear points in the mechanism of regulation of proliferation and differentiation.On the other hand, the central nervous system has a mechanism in which nerve axon regeneration is inhibited.
The research group focused on a protein called CRMP2 that phosphorylates on the nerve cell side when the central nervous system is damaged. CRMP2 is one of the microtubule-associated proteins that binds to microtubules in a non-phosphorylated state and promotes stabilization and polymerization of microtubules.It has been reported that genetically modified mice that suppress the phosphorylation of CRMP2, which was originally developed in the spinal cord injury model, have better recovery of motor function than wild-type mice.
In this study, we investigated whether suppression of CRMP2 phosphorylation is effective for nerve axon regeneration after injury using this genetically modified mouse in a model of optic nerve injury.As a result, microtubule depolymerization that occurred immediately after optic nerve injury was mild, and retinal ganglion cell shedding was small.It was also found that the expression of the nerve regeneration marker GAP43 was increased and that the nerve regeneration was remarkably promoted.
In the future, for ophthalmic diseases such as glaucoma and nervous system degenerative diseases such as ALS, which are considered to have the same pathological condition as optic nerve injury, the possibility of suppressing the progression of the disease by suppressing the phosphorylation of CRMP2 and the effectiveness of the CRMP2 phosphorylation inhibitor Regarding sex, it is necessary to verify using genetically modified mice.
Paper information:[Scientific Reports] Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury
