Compositions and methods related to tauopathy

摘要

Disclosed herein are isolated polypeptides, antibody preparations, treatment methods, diagnostic methods, and screening methods related to tauopathy. Generally, the isolated polypeptide includes a core pentapeptide, with the proviso that the isolated polypeptide is not a native full-length tau protein. Generally, the antibody preparations include antibody that specifically binds to SEQ ID NO:12. Generally, the treatment methods include administering to a subject a composition that includes the isolated polypeptide. Generally, the diagnostic methods includes contacting a sample from a subject with an antibody preparation that includes antibody that specifically binds to SEQ ID NO:12, and then detecting a ligand in the sample that specifically binds the antibody preparation. Generally, the screening method includes incubating a mixture of caspase-2, a labeled caspase-2 cleavage substrate, and a test compound under conditions effective to permit the caspase-2 to cleave the caspase-2 cleavage substrate, then determining whether the test compound inhibits cleavage of the substrate by caspase-2.

主权项

1. An isolated polypeptide comprising a core pentapeptide sequence having the formula aa5-aa4-aa3-aa2-aa1, wherein:
aa5 is tyrosine or phenylalanine; aa4 is lysine, aspartic acid, serine, or cysteine; aa3 is proline or valine; aa2 is valine, phenylalanine, alanine, or tyrosine; and aa1 is aspartic acid; with the proviso that the isolated polypeptide is not a native full-length tau protein; the N-terminal amino acid of the polypeptide is modified to comprise a methyl group or a benzyl group; and the C-terminal amino acid of the polypeptide is modified to comprise an aldehyde.