A synthetic peptide corresponding to a region of the human pericentriolar material 1 (PCM‐1) protein binds β‐amyloid (Aβ1‐42) oligomers. (18th March 2013)

• Record Type: Journal Article
• Authors: Chakravarthy, Balu; Ménard, Michel; Brown, Leslie; Hewitt, Melissa; Atkinson, Trevor; Whitfield, James
• Is Part Of: Journal of neurochemistry. Volume 126:Number 3(2013:Aug.)
• Page Start: 415
• Page End: 424
• Publication Date: 2013-03-18
• Subjects: Alzheimer's disease -- Aβ1‐42 oligomers -- Aβ‐binding peptides -- PCM‐1 protein; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12208
• Languages: English
• ISSNs: 0022-3042

Abstract

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 Aβ1‐42, 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 Aβ1‐42 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. Abstract : We have synthesized a ~ 5 kDa Aβ binding peptide (ABP‐p‐4‐5), a derivative of the human pericentriolar material‐1 protein that is involved in cell cycle transit and neurogenesis. ABP‐p‐4‐5 selectively binds with high affinity Aβ1‐42 oligomers that are believed to be the toxic drivers of AD (Alzheimer's disease). These observations suggest that ABP‐p‐4‐5 peptide may prove to be an AD therapeutic.