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

Uncontrolled aggregation of amyloid beta peptide (A?) is the main cause of Alzheimer's Disease. Therapeutic approaches of intervention in amyloid diseases include the use of small molecules able to stabilize the soluble A? conformation, or to redirect the amyloidogenic pathway towards non-toxic and non-fibrillar states. Fluorometric measurements revealed that the 3-(4'-trifluoromethylphenyl)-5-(4'-methoxyphenyl)-1,2,4-oxadiazole, when irradiated, is able to interact with monomeric A? peptide readdressing the aggregation pathway toward the formation of amorphous aggregates as evidenced by means of CD, AFM, and SAXS measurements. We hypothesize that this compound, under radiation, forms a reactive intermediate that sticks on the A? 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?. This finding should be the starting point to build new innovative therapies against Alzheimer's Disease