Reference - Detail
|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|
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.
|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|
|Human and Animal Cells||PC-12(RCB0009)|