| First Author | Chakravarthy B | Year | 2013 |
| Journal | J Neurochem | Volume | 126 |
| Issue | 3 | Pages | 415-24 |
| PubMed ID | 23432034 | Mgi Jnum | J:199628 |
| Mgi Id | MGI:5503298 | Doi | 10.1111/jnc.12208 |
| Citation | Chakravarthy B, et al. (2013) A synthetic peptide corresponding to a region of the human pericentriolar material 1 (PCM-1) protein binds beta-amyloid (Abeta1-42 ) oligomers. J Neurochem 126(3):415-24 |
| abstractText | 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-beta peptide (Abeta)1-42 with high affinity. Most importantly, a PCM-1-selective antibody co-precipitated Abeta and amyloid beta precursor protein (AbetaPP) from cerebral cortices and hippocampi from AD (Alzheimer's disease) transgenic mice that produce human AbetaPP and Abeta1-42 , suggesting that PCM-1 may interact with amyloid precursor protein/Abeta in vivo. We have identified rPK-4's Abeta-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 Abeta1-42 at nM levels. Most importantly, ABP-p4-5, like rPK-4, appears to preferentially bind Abeta1-42 oligomers, believed to be the toxic AD-drivers. As expected from these observations, ABP-p4-5 prevented Abeta1-42 from killing human SH-SY5Y neuroblastoma cells via apoptosis. These findings indicate that ABP-p4-5 is a possible candidate therapeutic for AD. |
