Final Report Summary - EGCG+INSULIN= (Towards construction of a comprehensive map of amyloid-ligand interactions: (-)-Epigallocatechin 3-Gallate and insulin amyloid)
The Marie Curie grant enabled the researcher to start a new research theme – biophysical studies of amyloid-like fibril formation and testing of potential antiamyloidogenic compounds. The institute did not carry out research in this field prior to the scientist's return. Together with the help of EU structural funds, European Social Fund, and Research Council of Lithuania new equipment and research reagents were purchased. One permanent staff position was established and supported by Lithuanian state budget; two additional staff positions (one of postdoc level and one of technician level) and two PhD students are supported by grants, obtained by Dr. V.Smirnovas. Eighteen undergraduate and six master’s students were/are volunteering in the group and were/are trained by the scientist.
The initial idea of the project was studying inhibition of insulin amyloid-like fibril formation by epigallocatechin gallate (EGCG). Surprisingly, it was found that, contrary to previously published data, EGCG does not inhibit insulin amyloid fibril formation. It led to the expansion of the project towards other amyloidogenic proteins and potential small molecule inhibitors. Within the scope of this project and the other projects, obtained by Dr. V.Smirnovas 265 compounds were tested as possible inhibitors of insulin, amyloid beta (Abeta), alpha-synuclein, and mouse prion protein (MoPrP) amyloid-like fibril formation. Five were identified as outstanding inhibitors of insulin fibril formation; four of them inhibited fibrillation of alpha-synuclein, one slowed down aggregation of MoPrP, but none were effective against Abeta.