Nogo receptor-mediated blockade of axonal growth
AssigneeYale University
InventorStephen M. Strittmatter
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Abstract
Disclosed are NgR proteins and biologically active Nogo (ligand) protein fragments. Also disclosed are compositions and methods for modulating the expression or activity of the Nogo and NgR protein. Also disclosed are peptides which block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.
Claims50
An isolated polypeptide comprising an amino acid sequence that is at least 80% identical to amino acids 27–309 of SEQ ID NO:2, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide consisting essentially of amino acids 27 to 309 of SEQ ID NO:2, except for it 20 conservative amino acid substitutions, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated soluble polypeptide comprising an ectodomain fragment of SEQ ID NO:2, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide fragment consisting of at least 35 consecutive amino acids of amino acids 1 to 445 of SEQ ID NO:2, wherein said polypeptide fragment inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide comprising amino acids 27 to 309 of SEQ ID NO:2, fused to a heterologous polypeptide;
- wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide comprising (a) an amino acid sequence that is at least 80% identical to amino acids 27–309 of SEQ ID NO:2;
- and (b) a heterologous polypeptide fused thereto, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide consisting essentially of an amino acid sequence at least 80% identical to amino acids 1 to 348 of SEQ ID NO:2, wherein said polypeptide inhibits NOGO receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide comprising amino acids 1 to 348 of SEQ ID NO:2, fused to a heterologous polypeptide;
- wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide comprising:
- (a) an amino acid sequence that is at least 80% identical to amino acids 1 to 348 of SEQ ID NO:2;
- and (b) a heterologous polypeptide fused thereto, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated soluble ectodomain fragment of NgR comprising at least 35 consecutive amino acids of amino acids 1 to 348 of SEQ lID NO:2, wherein said ectodomain fragment inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
An isolated polypeptide consisting essentially of an amino acid sequence that is at least 80% identical to amino acids 27–445 of SEQ ID NO:2, wherein said polypeptide inhibits NOGO-receptor-mediated neurite outgrowth inhibition.
Dependencies are inferred from the claim text.