So has anything here been put into clinical practice after 15 years studying this? We need axonal regeneration. Is this a piece of the stroke strategy? WHOM is making sure this gets translated into viable clinical interventions?
A Go on NOGO: Promising Therapy for CNS Disease and Injury
Cecilia Reyes and Yaroslav VoroninDepartment of Biology
Lake Forest College
Lake Forest, Illinois 60045
Abstract
Mammals have evolved with a limited capacity to regenerate neurons in the CNS. Damage to the CNS by traumatic injury, stroke and neurodegenerative disorders can result in permanent loss of sensory, motor, and cognitive functions. Fifteen years ago, my lab began studying the inhibitory mechanisms in damaged CNS. We have identified the myelin-associated protein Nogo-A as a key player in sprouting inhibition. Nogo-A, as well as two other inhibitory proteins, MAG and OMgp, bind to the nogo-66 receptor (NgR) to inhibit axonal regeneration in the CNS. We identified two mechanisms with neurons that promote Nogo-based CNS inhibition: the rho-ROCK kinase pathway that is selectively activated by NgR, and the integrin-actin pathway that is activated by a 66-amino-acid residue on Nogo-A. While genetic and chemical disruption of NgR ligands (nogo-A, MAG and OMgp) has resulted in poor regeneration after injury, manipulation of NgR has shown promising therapeutic value in both in vivo and in vitro. Therapeutic administration of NgR(310)ecto-Fc protein, an NgR antagonist, in tissue and mouse models can neutralize the inhibitory effects of the three NgR ligands and has proven beneficial in
promoting motor function after spinal cord injury and stroke. Finally, we have found that inhibiting Nogo-A in ALS and Alzheimer’s disease models reduces pathological characteristics, indicating that manipulating Nogo-NgR based inhibition holds great promise for CNS injury
and neurodegenerative disease.
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