| Subject | amyloid beta protein[1-42]; oligomer; pericentriolar material 1 protein; polypeptide; unclassified drug; Alzheimer disease; apoptosis; dot hybridization; enzyme linked immunosorbent assay; human cell; neuroblastoma cell; polyacrylamide gel electrophoresis; protein binding; Aβ-binding peptides; Aβ1-42 oligomers; Alzheimer's disease; PCM-1 protein; Amino Acid Sequence; Amyloid beta-Peptides; Autoantigens; Blotting, Western; Cell Cycle Proteins; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Immunoblotting; Immunoprecipitation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Peptides; Protein Structure, Tertiary; Mus musculus |
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| Abstract | We have recently reported that a ~19-kDa polypeptide, rPK-4, is a protein kinase Cs inhibitor that is 89% homologous to the 1171-1323 amino acid region of the 228-kDa human pericentriolar material-1 (PCM-1) protein (Chakravarthy et al. 2012). We have now discovered that rPK-4 binds oligomeric amyloid-β peptide (Aβ)1-42 with high affinity. Most importantly, a PCM-1-selective antibody co-precipitated Aβ and amyloid β precursor protein (AβPP) from cerebral cortices and hippocampi from AD (Alzheimer's disease) transgenic mice that produce human AβPP and Aβ 1-42, suggesting that PCM-1 may interact with amyloid precursor protein/Aβ in vivo. We have identified rPK-4′s Aβ-binding domain using a set of overlapping synthetic peptides. We have found with ELISA, dot-blot, and polyacrylamide gel electrophoresis techniques that a ~ 5 kDa synthetic peptide, amyloid binding peptide (ABP)-p4-5 binds Aβ 1-42 at nM levels. Most importantly, ABP-p4-5, like rPK-4, appears to preferentially bind Aβ1-42 oligomers, believed to be the toxic AD-drivers. As expected from these observations, ABP-p4-5 prevented Aβ1-42 from killing human SH-SY5Y neuroblastoma cells via apoptosis. These findings indicate that ABP-p4-5 is a possible candidate therapeutic for AD. © Her Majesty the Queen in Right of Canada 2013. |
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