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IMPRiND SIGNED

Inhibiting Misfolded protein PRopagation in Neurodegenerative Diseases - Sofia ref.: 116060

Total Cost €

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EC-Contrib. €

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Partnership

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 IMPRiND project word cloud

Explore the words cloud of the IMPRiND project. It provides you a very rough idea of what is the project "IMPRiND" about.

transfer    species    relevance    imprind    resemblance    prion    networks    entire    na    cells    models    synuclein    toxicity    laboratories    bimolecular    fibril    burden    oligomeric    accelerate    standardise    effects    transplantation    human    spread    interfere    homogeneous    assay    assemblies    unprecedented    effort    parkinson    milieu    correlate    met    pathological    cultures    propagation    ve    ipsc    neuronal    generate    animal    labelled    fluorescently    directions    modifiers    biological    vitro    miniaturise    live    progression    pipeline    interventions    stage    misfolded    markers    organotypic    oligomerisation    tau    broadly    native    untagged    functional    construct    map    proteotoxicity    readouts    alpha    proteostatic    cellular    synergistically    clinical    neurodegenerative    content    microdialysis    animals    pathogenic    validation    alzheimer    fluorescence    events    tractability    complementation    populations    secretion    suitable    druggability    interconnected    iuml    assays    critical    humans    imprint    imaging    screens    calls    pharmaceutical    disease    shown    examine    vivo    molecular    ambition    monitor    meet    suggesting    industry    situ    brain    clearance    therapeutic    protection    progress    neurons    peripheral   

Project "IMPRiND" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website http://imprind.org/
 Total cost 11˙363˙398 €
 EC max contribution 4˙684˙998 € (41%)
 Programme 1. H2020-EU.3.1.7. (Innovative Medicines Initiative 2 (IMI2))
 Code Call H2020-JTI-IMI2-2015-07-two-stage
 Funding Scheme IMI2-RIA
 Starting year 2017
 Duration (year-month-day) from 2017-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 865˙686.00
2    DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV DE (BONN) participant 835˙625.00
3    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) participant 652˙330.00
4    UNIVERSITE DE BORDEAUX FR (BORDEAUX) participant 505˙000.00
5    VIB VZW BE (ZWIJNAARDE - GENT) participant 420˙000.00
6    IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON EL (ATHINA) participant 360˙000.00
7    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) participant 327˙000.00
8    UNITED KINGDOM RESEARCH AND INNOVATION UK (SWINDON) participant 240˙207.00
9    UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS DE (GOETTINGEN) participant 217˙000.00
10    AARHUS UNIVERSITET DK (AARHUS C) participant 208˙000.00
11    UNIVERSITY OF DUNDEE UK (DUNDEE) participant 54˙150.00
12    AbbVie Ltd UK (Maidenhead) participant 0.00
13    Eli Lilly and Company Limited UK (Basingstoke) participant 0.00
14    H. LUNDBECK AS DK (VALBY) participant 0.00
15    INSTITUT DE RECHERCHES SERVIER FR (SURESNES) participant 0.00
16    JANSSEN PHARMACEUTICA NV BE (BEERSE) participant 0.00
17    MEDICAL RESEARCH COUNCIL UK (SWINDON) participant 0.00
18    NOVARTIS PHARMA AG CH (BASEL) participant 0.00
19    SCIPROM SARL CH (SAINT SULPICE) participant 0.00

Map

 Project 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.

 Deliverables

List of deliverables.
Launch of website, Twitter and other dissemination activities Documents, reports 2020-01-22 14:45:24
Press release Documents, reports 2020-01-22 14:45:24

Take a look to the deliverables list in detail:  detailed list of IMPRiND deliverables.

 Publications

year authors and title journal last update
List of publications.
2019 Parvez Alam, Luc Bousset, Ronald Melki, Daniel E. Otzen
α‐synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities
published pages: 522-534, ISSN: 0022-3042, DOI: 10.1111/jnc.14808
Journal of Neurochemistry 150/5 2020-04-01
2019 Audrey Chabrat, Emmanuelle Lacassagne, Rodolphe Billiras, Sophie Landron, Amélie Pontisso-Mahout, Hélène Darville, Alain Dupront, Francis Coge, Esther Schenker, David Piwnica, Emmanuel Nivet, François Féron, Clotilde Mannoury la Cour
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons
published pages: 1-15, ISSN: 1687-966X, DOI: 10.1155/2019/2945435
Stem Cells International 2019 2020-04-01
2019 Taxiarchis Katsinelos, Benjamin J. Tuck, Aamir S. Mukadam, William A. McEwan
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.01139
Frontiers in Immunology 10 2020-04-01
2019 Leonidas Stefanis, Evangelia Emmanouilidou, Marina Pantazopoulou, Deniz Kirik, Kostas Vekrellis, George K. Tofaris
How is alpha‐synuclein cleared from the cell?
published pages: 577-590, ISSN: 0022-3042, DOI: 10.1111/jnc.14704
Journal of Neurochemistry 150/5 2020-04-01
2020 Josquin Courte, Luc Bousset, Ysander Von Boxberg, Catherine Villard, Ronald Melki, Jean-Michel Peyrin
The expression level of alpha-synuclein in different neuronal populations is the primary determinant of its prion-like seeding
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-020-61757-x
Scientific Reports 10/1 2020-04-01
2019 Guerrero-Ferreira, Ricardo; Taylor, Nicholas MI; Arteni, Ana-Andreea; Kumari, Pratibha; Mona, Daniel; Ringler, Philippe; Britschgi, Markus; Lauer, Matthias E; Makky, Ali; Verasdonck, Joeri; Riek, Roland; Melki, Ronald; Meier, Beat H; Böckmann, Anja; Bousset, Luc; Stahlberg, Henning
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy
published pages: , ISSN: 2050-084X, DOI: 10.3929/ethz-b-000391777
EISSN: 2050-084X 1 2020-04-01
2020 Francesca De Giorgi, Florent Laferrière, Federica Zinghirino, Emilie Faggiani, Alons Lends, Mathilde Bertoni, Xuan Yu, Axelle Grélard, Estelle Morvan, Birgit Habenstein, Nathalie Dutheil, Evelyne Doudnikoff, Jonathan Daniel, Stéphane Claverol, Chuan Qin, Antoine Loquet, Erwan Bezard, François Ichas
Emergence of stealth polymorphs that escape α-synuclein amyloid monitoring, take over and acutely spread in neurons
published pages: , ISSN: 2041-1723, DOI: 10.1101/2020.02.11.943670
Nature Comunication 2020-04-01
2020 Amulya Nidhi Shrivastava, Luc Bousset, Marianne Renner, Virginie Redeker, Jimmy Savistchenko, Antoine Triller, Ronald Melki
Differential Membrane Binding and Seeding of Distinct α-Synuclein Fibrillar Polymorphs
published pages: , ISSN: 0006-3495, DOI: 10.1016/j.bpj.2020.01.022
Biophysical Journal 2020-04-01
2019 Wenjuan Zhang, Benjamin Falcon, Alexey G Murzin, Juan Fan, R Anthony Crowther, Michel Goedert, Sjors HW Scheres
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases
published pages: , ISSN: 2050-084X, DOI: 10.1101/468892
Elife 2020-04-01
2019 Nolwen L. Rey, Luc Bousset, Sonia George, Zachary Madaj, Lindsay Meyerdirk, Emily Schulz, Jennifer A. Steiner, Ronald Melki, Patrik Brundin
α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb
published pages: , ISSN: 2051-5960, DOI: 10.1186/s40478-019-0859-3
Acta Neuropathologica Communications 7/1 2020-04-01
2020 Antonio Dominguez-Meijide1, Eftychia Vasili, Annekatrin König, Maria-Sol Cima-Omori, Andrei Leonov, Sergey Ryazanov, Markus Zweckstetter, Christian Griesinger, Tiago F. Outeiro
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization
published pages: , ISSN: , DOI: 10.1101/2020.01.27.921643
2020-04-01
2019 Alexis Fenyi, Laurène Leclair-Visonneau, Thomas Clairembault, Emmanuel Coron, Michel Neunlist, Ronald Melki, Pascal Derkinderen, Luc Bousset
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification
published pages: 38-43, ISSN: 0969-9961, DOI: 10.1016/j.nbd.2019.05.002
Neurobiology of Disease 129 2020-04-01
2020 Wenjuan Zhang, Airi Tarutani, Kathy L. Newell, Alexey G. Murzin, Tomoyasu Matsubara, Benjamin Falcon, Ruben Vidal, Holly J. Garringer, Yang Shi, Takeshi Ikeuchi, Shigeo Murayama, Bernardino Ghetti, Masato Hasegawa, Michel Goedert, Sjors H.W. Scheres
Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathy
published pages: , ISSN: 2041-1723, DOI: 10.1101/811703
Nature 2020-04-01
2018 Alexis Fenyi, Audrey Coens, Tracy Bellande, Ronald Melki, Luc Bousset
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-28856-2
Scientific Reports 8/1 2020-01-22
2019 Panagiota Mavroeidi, Fedra Arvanitaki, Anastasia-Kiriaki Karakitsou, Maria Vetsi, Ismini Kloukina, Markus Zweckstetter, Karin Giller, Stefan Becker, Zachary A. Sorrentino, Benoit I. Giasson, Poul Henning Jensen, Leonidas Stefanis, Maria Xilouri
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models
published pages: , ISSN: 0001-6322, DOI: 10.1007/s00401-019-02014-y
Acta Neuropathologica 2020-01-22
2019 Eftychia Vasili, Antonio Dominguez-Meijide, Tiago Fleming Outeiro
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved
published pages: , ISSN: 1662-5099, DOI: 10.3389/fnmol.2019.00107
Frontiers in Molecular Neuroscience 12 2020-01-22
2019 Gregor Bieri, Michel Brahic, Luc Bousset, Julien Couthouis, Nicholas J. Kramer, Rosanna Ma, Lisa Nakayama, Marie Monbureau, Erwin Defensor, Birgitt Schüle, Mehrdad Shamloo, Ronald Melki, Aaron D. Gitler
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons
published pages: , ISSN: 0001-6322, DOI: 10.1007/s00401-019-01995-0
Acta Neuropathologica 2020-01-22
2018 Benjamin Falcon, Wenjuan Zhang, Alexey G. Murzin, Garib Murshudov, Holly J. Garringer, Ruben Vidal, R. Anthony Crowther, Bernardino Ghetti, Sjors H. W. Scheres, Michel Goedert
Structures of filaments from Pick’s disease reveal a novel tau protein fold
published pages: 137-140, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0454-y
Nature 561/7721 2020-01-22
2018 Benjamin Falcon, Wenjuan Zhang, Manuel Schweighauser, Alexey G. Murzin, Ruben Vidal, Holly J. Garringer, Bernardino Ghetti, Sjors H. W. Scheres, Michel Goedert
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold
published pages: 699-708, ISSN: 0001-6322, DOI: 10.1007/s00401-018-1914-z
Acta Neuropathologica 136/5 2020-01-22
2019 Amulya Nidhi Shrivastava, Virginie Redeker, Laura Pieri, Luc Bousset, Marianne Renner, Karine Madiona, Caroline Mailhes‐Hamon, Audrey Coens, Luc Buée, Philippe Hantraye, Antoine Triller, Ronald Melki
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na + /K + ‐ATPase and AMPA receptors
published pages: e99871, ISSN: 0261-4189, DOI: 10.15252/embj.201899871
The EMBO Journal 38/3 2020-01-22
2019 Simona Gribaudo, Philippe Tixador, Luc Bousset, Alexis Fenyi, Patricia Lino, Ronald Melki, Jean-Michel Peyrin, Anselme L. Perrier
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network
published pages: 230-244, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2018.12.007
Stem Cell Reports 12/2 2020-01-22
2018 Maria Grazia Spillantini, Michel Goedert
Neurodegeneration and the ordered assembly of α-synuclein
published pages: 137-148, ISSN: 0302-766X, DOI: 10.1007/s00441-017-2706-9
Cell and Tissue Research 373/1 2020-01-22
2018 Michel Goedert, Yoshiki Yamaguchi, Sushil K. Mishra, Makoto Higuchi, Naruhiko Sahara
Tau Filaments and the Development of Positron Emission Tomography Tracers
published pages: , ISSN: 1664-2295, DOI: 10.3389/fneur.2018.00070
Frontiers in Neurology 9 2020-01-22
2017 Anthony W. P. Fitzpatrick, Benjamin Falcon, Shaoda He, Alexey G. Murzin, Garib Murshudov, Holly J. Garringer, R. Anthony Crowther, Bernardino Ghetti, Michel Goedert, Sjors H. W. Scheres
Cryo-EM structures of tau filaments from Alzheimer’s disease
published pages: 185-190, ISSN: 0028-0836, DOI: 10.1038/nature23002
Nature 547/7662 2020-01-22
2017 George K. Tofaris
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease
published pages: 569-576, ISSN: 1877-7171, DOI: 10.3233/JPD-171176
Journal of Parkinson\'s Disease 7/4 2020-01-22
2018 Franziska Kundel, Liu Hong, Benjamin Falcon, William A. McEwan, Thomas C. T. Michaels, Georg Meisl, Noemi Esteras, Andrey Y. Abramov, Tuomas J. P. Knowles, Michel Goedert, David Klenerman
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading
published pages: , ISSN: 1948-7193, DOI: 10.1021/acschemneuro.8b00094
ACS Chemical Neuroscience 2020-01-22

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