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H2020Staff exchange2020–2025

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

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-01-01 → 2025-06-30
EU contribution
€1,058,000
Participants
14
Scheme
MSCA-RISE

Lines connect the coordinator with its partners.

Results in brief

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

Neurodegenerative diseases represent a large burden to healthcare systems worldwide. The common denominator of neurodegeneration is the presence of misfolded and aggregated forms of specific proteins, which are suspected to be the culprits of disease progression. Neuronal protein tau is found aggregated in the most severe neurodegenerative tauopathies including Alzheimer's disease (AD). In the project we aimed to monitor conformation changes within the Tau protein variants that lead to its pathological forms characteristic in AD. The detailed characterization of conformational changes of Tau protein towards its pathological forms will provide the basis for novel diagnostic and therapeutic strategies for AD and other tauopathies. There are two overall project objectives: i) To delineate pathways underlying pathologic tau polymerization, taking advantage of synergy created by the multidisciplinary InterTau network ii) To establish a collaborative structure-characterizing platform based on existing and newly created tools to identify innovative interventional and diagnostics targets in the tau assembly cascade After fruitful collaboration between project partners over more than five years of project duration, reflected by 12 publications, we contributed to better description of tau conformational and chemical changes leading to its aggregation and uncovered novel properties of nervous system underlying tau pathology propagation/healing.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • Masarykova univerzita · BrnoCoordinatorCzechia
  • AXON NEUROSCIENCE R&D SERVICES SE · BRATISLAVASlovakia
  • BIOVENDOR LABORATORNI MEDICINA SRO · BRNOCzechia
  • DATAMEDRIX GMBH · WIENAustria
  • GENETON S.R.O. · BratislavaSlovakia
  • LATVIJAS ORGANISKAS SINTEZES INSTITUTS · RigaLatvia
  • NEUROIMUNOLOGICKY USTAV SLOVENSKEJ AKADEMIE VIED, v. v. i. · BRATISLAVASlovakia
  • OREGON STATE UNIVERSITY · CORVALLISUnited States
  • Omiics ApS · Aarhus NDenmark
  • ROYAL COLLEGE OF SURGEONS IN IRELAND · DUBLIN 2Ireland
  • UNIVERSIDAD NACIONAL DE CUYO · MendozaArgentina
  • UNIVERSITAS SANATA DHARMA · YogyakartaIndonesia
  • UNIVERSITY HEALTH NETWORK · TorontoCanada
  • UNIVERSITY OF PITTSBURGH · PittsburghUnited States

Links

Data: CORDIS, © European Union