Photo-inhibition of A beta fibrillation mediated by a newly designed fluorinated oxadiazole

摘要

Uncontrolled aggregation of amyloid beta peptide (A beta) is the main cause of Alzheimer's disease. Therapeutic approaches to intervention in amyloid diseases include the use of small molecules able to stabilize the soluble A beta conformation, or to redirect the amyloidogenic pathway towards non-toxic and non-fibrillar states. Fluorometric measurements revealed that 3-(4'-trifluoromethylphenyl)-5-(4'methoxyphenyl)-1,2,4-oxadiazole, when irradiated, is able to interact with the monomeric A beta peptide readdressing the aggregation pathway toward the formation of amorphous aggregates as evidenced by CD, AFM, and SAXS measurements. We hypothesize that this compound, under radiation, forms a reactive intermediate that sticks on the A beta peptide by interfering with its fibrillation process. Cytotoxicity assays performed on LAN5 neuroblastoma cells suggest that the presence of oxadiazole reduces the toxicity of A beta. This finding might be the start of innovative therapies against Alzheimer's disease.