Descrizione del progetto
La conformazione della proteina tau come bersaglio terapeutico nella malattia di Alzheimer
Le proteine tau abbondano nei neuroni del sistema nervoso centrale e si esprimono a livelli molto bassi negli astrociti e negli oligodendrociti, fornendo la stabilizzazione dei microtubuli. Le patologie legate alle proteine tau, tra cui il morbo di Alzheimer, sono associate a cambiamenti conformazionali durante la oligomerizzazione e l’assemblaggio, con conseguente tossicità cellulare. Le proteine tau in conformazione alterata potrebbero essere un promettente bersaglio molecolare per una terapia che modifichi la malattia. L’obiettivo principale del progetto InterTAU, finanziato dall’UE, è quello di studiare la struttura dettagliata delle proteine tau e le loro varianti negli stati monomerici, oligomerici e fibrillari rilevanti per le malattie. Il consorzio internazionale InterTAU comprende un’azienda biotecnologica in ambito clinico che si dedica allo sviluppo dell’immunoterapia anti-tau e partner accademici con metodologie adeguate per la caratterizzazione funzionale e strutturale della via di modificazione delle proteine tau attraverso la risonanza magnetica nucleare, la microscopia crio-elettronica e i test cellulari.
Obiettivo
There is an enormous and unmet medical need to find efficient methods of prevention, diagnosis and disease- modifying therapies for neurodegenerative disorders, including Alzheimer’s disease (AD), other tauopathies and Parkinson’s disease (PD). The common molecular denominator of tauopathies are pathological forms of tau protein, and in Parkinson’s disease these are pathological forms of -synuclein. Moreover, -synuclein has a distinct role in pathophysiology of tauopathies, mainly in tau hyperphosphorylation and aggregation, and vice versa. Tau pathology relates to conformational changes during oligomerization and assembly resulting in toxicity. Given their role in the pathogenesis, conformationally altered and assembled tau or -synuclein would be a promising molecular target for disease-modifying therapies. However, the field is still lacking a deeper understanding of associated structural changes in the course of assembly and their inducers on the pathway towards pathological forms of these proteins; therefore, the pharma development is hampered. The main aim of the InterTau project is the detailed structural and biophysical characterization of tau and -synuclein -synuclein protein and their variants in monomeric, oligomeric and fibrillar states relevant for AD, other tauopathies. The InterTAU consortium is composed 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 biotech through the non-academic partner. The platform for sharing knowledge will be a foundation of sustainable cooperation beyond the InterTau project.
Campo scientifico
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- natural sciencesbiological sciencesmolecular biologystructural biology
Parole chiave
Programma(i)
Meccanismo di finanziamento
MSCA-RISE - Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE)Coordinatore
601 77 Brno
Cechia