Objective
Assemblies of tau and α-synuclein were shown to spread along interconnected neuronal networks suggesting broadly relevant therapeutic directions for Alzheimer’s and Parkinson’s disease. This requires a pre-clinical stage of development that has yet to be met. The scale of neurodegenerative disease burden in Europe calls for an unprecedented research effort that can only be achieved through collaboration between leading European laboratories and the pharmaceutical industry. To meet this ambition the IMPRiND consortium will synergistically accelerate progress to map and target critical steps in the propagation, proteostatic response and protection against misfolded α-synuclein and tau. Specifically we aim to (1) identify disease-relevant assemblies, imprint their biological properties in vitro and generate homogeneous populations to assay and interfere with their pathogenic effects; (2) develop and miniaturise assays to monitor secretion, uptake, clearance and oligomerisation using bimolecular fluorescence complementation of oligomeric species or transfer of untagged assemblies to fluorescently labelled fibril-naïve cells and measure markers of early proteotoxicity that are suitable for live imaging high content screens; (3) deliver robust validation assays for these molecular events in complex cellular systems with greater functional resemblance to the native milieu of the brain such as iPSC-based and organotypic cultures (4) standardise pathological readouts in animal models for in vivo validation of modifiers, correlate them with novel peripheral or in situ markers using microdialysis to accelerate the assessment of therapeutic interventions and relevance to humans, e.g. by transplantation of human iPSC neurons in animals; (5) assess toxicity and druggability of potential targets. IMPRiND will construct this entire pipeline to examine the prion-like properties of α-synuclein and tau and test their tractability against disease progression.
Fields of science
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- social sciencessociologygovernancepublic services
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicineneurologyparkinson
- medical and health sciencesclinical medicinetransplantation
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
OX1 2JD Oxford
United Kingdom
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Participants (18)
2500 Valby
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CB2 1TN Cambridge
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SN2 1FL Swindon
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115 27 Athina
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37075 Goettingen
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33000 Bordeaux
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
75654 Paris
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Participation ended
8000 Aarhus C
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75794 Paris
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Participation ended
DD1 4HN Dundee
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9052 ZWIJNAARDE - GENT
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53127 Bonn
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2340 Beerse
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4056 Basel
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91190 GIF-SUR-YVETTE
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RG21 4FA Basingstoke
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1025 Saint Sulpice
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
65205 Wiesbaden
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