Integrative structural biology of pathological tau protein, an appealing therapeutic target for Alzheimer´s disease modifying drugs

There is an enormous and unmet medical need to find efficient methods of prevention, diagnosis and disease-modifying therapies for tauopathies, including Alzheimer’s disease. The common molecular denominator of tauopathies are pathological forms of tau protein. Tau pathology relates to conformational changes during oligomerization and assembly resulting in toxicity. Given its role in the pathogenesis, conformationally altered and assembled tau would be a promising molecular target for disease-modifying therapy. However, the field is still lacking a deeper understanding of tau structural changes in the course of assembly and their inducers on the pathway towards the pathological forms of Tau; therefore, the pharma development is hampered. The main aim of the InterTau project is the detailed structural and biophysical characterization of tau protein and its variants in monomeric, oligomeric and fibrillar states relevant for AD and other tauopathies. The InterTAU consortium is composed of a clinical-stage biotech company pursuing development of anti-tau immunotherapy and academic partners with cutting-edge methodologies suitable for functional and structural characterization of the tau assembly pathway by solution and solid-state nuclear magnetic resonance (NMR), cryo-electron microscopy and cellular assays corroborated by bioinformatics. The mutual transfer of complementary expertise envisaged in the project will facilitate academic outcome and biotechnological development. Specific expertise will be transferred from three institutions in North America and one institution from Argentina. The results of InterTAU will be directly translated into innovation in pharmacological development through the non-academic partner. The platform for sharing knowledge will be a foundation of sustainable cooperation beyond the InterTau project.