Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc, 779 00 Olomouc
International Clinical Research Centre, St. Anne’s University Hospital Brno
Research objectives:
– To screen two chemical libraries of approved drugs (drug repurposing) and new chemical entities from the IMTM compound collection (>120k compounds) by a peptide-based high throughput-compatible tau aggregation assay.
– How the identified hits affect the biochemical, biophysical and structural properties of tau, crucial for aggregation and propagation, will be performed using biochemical and biophysical approaches and atomic force and transmission electron microscopy.
– Molecular dynamics simulations will be performed to identify if the hits interact with amyloid motifs or cysteine residues in tau and the potential mechanisms of anti-amyloidogenic effects
– Whether the identified hits abolish the formation of toxic, pathological prion-like aggregates will be examined by cellular seeding assays using human tauopathy post-mortem brain samples, tau-expressing cells and neural cultures derived from patient iPSCs to model tauopath