• Fibrils Detection
• Neurodegeneration
• Protein Misfolding
• Small Molecules Synthesis
• Tau protein
• Transthyretin

The project of this master thesis was carried on in collaboration with the Department of Pharmacy of Paris-Saclay University.
The work was focused on studying and preventing protein misfolding since it is correlated to neurodegenerative diseases onset and progression. The project was centred on two amyloidogenic proteins: Transthyretin (TTR) responsible of TTR-related amyloidosis (A-TTR), and Tau, one of the proteins involved in Alzheimer’s disease.
During the first three months of my stage in France, I set up some fluorescence assays to evaluate the aggregation of TTR and a fragment of Tau protein in the presence of potential inhibitors, using ThT as fluorescent dye.
In details, I analysed three series of small molecules, belonged to Pisa home-library, on TTR protein. For the most promising compounds I carried out 8-anilino-1-naphtalensulfonic acid (ANS) competitive binding assay to evaluate their IC50.
Moreover, during this period, I synthetised two fragments of Tau protein by solid phase synthesis, and I analysed their aggregation kinetics with ThT. One of them was used to screen some peptido-mimetics present in Paris-Saclay home-library and some ferulic-acid analogues belonged to Pisa home-library.
The promising results obtained on ferulic acid analogues led to the synthesis of new compounds inspired by natural ones. These compounds were prepared coupling some selected natural derivatives with an aromatic ring substituted in o, m, p position with CF3.
The synthesis and characterization of the new derivatives were carried out at Pisa University.