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Strong Inhibition of Beta‐Amyloid Peptide Aggregation Realized by Two‐Steps Evolved Peptides
Author(s) -
Ghimire Gautam Sunita,
Komatsu Masayuki,
Nishigaki Koichi
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12400
Subject(s) - peptide , thioflavin , in vitro , amyloid beta , chemistry , amyloid (mycology) , cytotoxic t cell , biochemistry , protein aggregation , beta (programming language) , alzheimer's disease , biophysics , disease , biology , medicine , pathology , inorganic chemistry , computer science , programming language
Several decades of cumulated research evidence have proven that aggregation of beta‐amyloid 42 (A β 42) is the main cause of neuronal death in the brains of patients with Alzheimer's disease. Therefore, inhibition of A β 42 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 K d in the n m range) for A β 42. Functionally, these peptides strongly inhibited the aggregation of A β 42 as shown by the thioflavin T assay and atomic force microscopy. Moreover, these peptides rescued PC 12 cells from the cytotoxic effect of aggregated A β 42 in vitro . Our results suggest that these novel peptides may be potential therapeutic seeds for the treatment of Alzheimer's disease.