The Nogo66 receptor pathway and CNS axon regeneration: new hopes for treating CNS injuries and neurodegeneration

Abstract

The neuronal leucine-rich repeat Nogo66 receptor (NgR) interacts with the myelin proteins Nogo66, myelin associated glycoprotein and oligodendrocyte myelin glycoprotein to inhibit axon growth. Modulation of these cell surface NgR-dependent interactions or the inhibitory intracellular signalling pathways may promote axon growth in the CNS after injury and present an attractive axon regeneration platform for treating CNS injuries or even neurodegenerative disorders. Multiple NgR antagonism approaches, including soluble NgR proteins, anti-NgR antibodies, a Nogo-derived antagonist peptide and NgR signal transduction modulators, have demonstrated striking efficacies in promoting functional recoveries in animal models of spinal cord injury, stroke and multiple sclerosis. This review summarises the neurobiology of the NgR pathway and the various drug discovery strategies that are specifically based on modulation of the myelin–NgR interaction.

Keywords::

• axon regeneration
• CNS myelin
• neurite sprouting
• Nogo66 receptor

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