NOGO RECEPTOR FUNCTIONAL MOTIFS, PEPTIDE MIMETICS, AND MUTATED FUNCTIONAL MOTIFS RELATED THERETO, AND METHODS OF USING THE SAME

摘要

The present invention provides novel isolated and purified polynucleotides and polypeptides related to functional motifs of the Nogo receptor 1 (NgR1) (e.g., the binding pocket on the side surface of NgR1, functional motifs comprising the amino acid sequence of FRG, etc.) and use of peptides mimicking these functional motifs as antagonists to NgR1 ligands, e.g., myelin-associated glycoprotein, oligodendrocyte myelin glycoprotein, Nogo-A, Nogo-66, GT1b, an antibody to Nogo receptor, an antibody to GT1b, an antibody to p75 neurotrophin receptor, and an antibody to Lingo-1, etc. The invention also provides antibodies to the mimetic peptide antagonists. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for treatments requiring axonal regeneration, i.e., reversal of the effects of NgR1 ligand binding to the NgR1 (i.e., producing inhibition of axonal growth). The present invention also is directed to novel methods for treating disorders arising from inhibition of axonal growth mediated by the binding of NgR1 ligands to the NgR1. Further, the invention is directed to methods of treating a subject with a neurodegenerative disorder, including, but not limited to, Parkinson's disease, Alzheimer's disease, progressive supranuclear palsy, multiple sclerosis, multiple system atrophy, corticobasal degeneration, Huntington's disease, dementia with Lewy bodies, spinocerebellar ataxia, stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, epilepsy, and senile dementia, comprising, e.g., antagonizing NgR1.