Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
OX1 2JD Oxford
Regno Unito
Mostra sulla mappa
Partecipanti (18)
2500 Valby
Mostra sulla mappa
CB2 1TN Cambridge
Mostra sulla mappa
SN2 1FL Swindon
Mostra sulla mappa
115 27 Athina
Mostra sulla mappa
37075 Goettingen
Mostra sulla mappa
33000 Bordeaux
Mostra sulla mappa
Soggetto giuridico diverso da un subappaltatore che è affiliato o legalmente collegato a un partecipante. Il soggetto svolge le attività secondo le condizioni stabilite nell’accordo di sovvenzione, fornisce beni o servizi per l’azione, ma non ha sottoscritto l’accordo di sovvenzione. Una terza parte rispetta le regole applicabili al suo partecipante correlato ai sensi dell’accordo di sovvenzione per quanto riguarda l’ammissibilità dei costi e il controllo delle spese.
75654 Paris
Mostra sulla mappa
Partecipazione conclusa
8000 Aarhus C
Mostra sulla mappa
75794 Paris
Mostra sulla mappa
Partecipazione conclusa
DD1 4HN Dundee
Mostra sulla mappa
9052 ZWIJNAARDE - GENT
Mostra sulla mappa
53127 Bonn
Mostra sulla mappa
2340 Beerse
Mostra sulla mappa
4056 Basel
Mostra sulla mappa
91190 GIF-SUR-YVETTE
Mostra sulla mappa
RG21 4FA Basingstoke
Mostra sulla mappa
1025 Saint Sulpice
Mostra sulla mappa
L’organizzazione si è definita una PMI (piccola e media impresa) al momento della firma dell’accordo di sovvenzione.
65205 Wiesbaden
Mostra sulla mappa