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P2‐366: Inhibition of Aβ production without perturbing Notch and Neuregulin signaling
Author(s) -
Tatsumi Shinichi,
Okochi Masayasu,
Tagami Shinji,
Itoh Naohiro,
Nishitomi Kouhei,
Jiang Jingwei,
Nakayama Taisuke,
Yanagida Kanta,
Kodama Takashi S.,
Mori Kohji,
Oguri Takashi,
Takeda Masatoshi
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1444
Subject(s) - notch signaling pathway , neuregulin , neuregulin 1 , amyloid precursor protein secretase , presenilin , microbiology and biotechnology , chemistry , extracellular , erbb4 , notch 1 , signal transduction , biology , amyloid precursor protein , disease , alzheimer's disease , medicine , receptor tyrosine kinase
biological activity. Methods: Affinity selection of random peptide displaying phage library was performed using the anti-fibril scFv, B6 as a mold at 3-rounds biopanning. The isolated phage clones were analyzed their motif DNA sequences by the ABI Genetic Analyzer PRISM 3100. The motif sequences were chemically synthesized and tested their effect on A 1-42 fibril formation by thioflavin T and precipitation assay (Yoshihara, et al., J. Biochem., 2, 2008). Results: We isolated phage clones from peptide phage display libraries and identified several different peptide motifs (B6L1, B6-L10 and B7-C15). The deduced amino acid sequences of these peptide motifs have little homology to A 1-42 peptide. The synthetic peptides based on these phage motifs (B6-L1, B7-C15) had inhibitory effect on A 1-42 fibrillation by binding to prefibrillar soluble oligomers. Conclusions: Taken these results together with the sequence homology analysis, it is suggested that B6-L1 and B7-C15 might be mimics of A 1-42 fibril. To investigate this possibility, we characterize the specificity of immune response elicited with these peptides in mice.