Premium
A synthetic peptide corresponding to a region of the human pericentriolar material 1 ( PCM ‐1) protein binds β‐amyloid (Aβ 1‐42 ) oligomers
Author(s) -
Chakravarthy Balu,
Ménard Michel,
Brown Leslie,
Hewitt Melissa,
Atkinson Trevor,
Whitfield James
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12208
Subject(s) - peptide , amyloid precursor protein , amyloid (mycology) , microbiology and biotechnology , p3 peptide , chemistry , biochemistry , western blot , genetically modified mouse , gel electrophoresis , polyacrylamide gel electrophoresis , alzheimer's disease , transgene , biology , gene , medicine , inorganic chemistry , disease , pathology , enzyme
We have recently reported that a ~19‐ kD a polypeptide, rPK ‐4, is a protein kinase Cs inhibitor that is 89% homologous to the 1171–1323 amino acid region of the 228‐ kD a 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 Aβ 1‐42 oligomers, believed to be the toxic AD‐drivers. As expected from these observations, ABP‐p4‐5 prevented Aβ 1‐42 from killing human SH‐SY5Y neuroblastoma cells via apoptosis. These findings indicate that ABP‐p4‐5 is a possible candidate therapeutic for AD.