RRC ID 36870
Author Ghimire Gautam S, Komatsu M, Nishigaki K.
Title Strong inhibition of beta-amyloid peptide aggregation realized by two-steps evolved peptides.
Journal Chem Biol Drug Des
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.
Volume 85(3)
Pages 356-68
Published 2015-3-1
DOI 10.1111/cbdd.12400
PMID 25082146
MeSH Amino Acid Sequence Amyloid beta-Peptides / chemistry Amyloid beta-Peptides / metabolism* Amyloid beta-Peptides / pharmacology Animals Cell Survival / drug effects Fluorescein / chemistry Kinetics Microscopy, Atomic Force Molecular Sequence Data PC12 Cells Peptide Fragments / chemistry Peptide Fragments / metabolism* Peptide Fragments / pharmacology Peptide Library Peptides / chemistry Peptides / metabolism* Peptides / pharmacology Protein Binding Rats Surface Plasmon Resonance
IF 2.256
Times Cited 3
Resource
Human and Animal Cells PC-12(RCB0009)