title: Strong inhibition of beta-amyloid peptide aggregation realized by two-steps evolved peptides.
abstract: Several decades of cumulated research evidence have proven that aggregation of beta-amyloid 42 (Aβ42) is the main cause of neuronal death in the brains of patients with Alzheimer's disease. Therefore, inhibition of Aβ42 aggregation holds great promise for the prevention and treatment of Alzheimer's disease. To this end, we used a systematic in vitro evolution including a paired peptide library method. We identified two peptides with high binding affinity (with Kd in the nm range) for Aβ42. Functionally, these peptides strongly inhibited the aggregation of Aβ42 as shown by the thioflavin T assay and atomic force microscopy. Moreover, these peptides rescued PC12 cells from the cytotoxic effect of aggregated Aβ42 in vitro. Our results suggest that these novel peptides may be potential therapeutic seeds for the treatment of Alzheimer's disease.
authors.affiliation: Department of Functional Materials Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-Ku, Saitama-Shi, 338-8570, Japan.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghimire Gautam
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishigaki
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019793:Fluorescein / Q000737:chemistry; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019151:Peptide Library; D010455:Peptides; C075222:amyloid beta-protein (1-42); D019793:Fluorescein
keywords: Alzheimer's disease; aggregation; aggregation inhibitors; amyloid; amyloid precursor protein; aptamers; fibrillization; in vitro evolution; mRNA display; peptide aptamers