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Name IMPRiND
Long Name Inhibiting misfolded protein propagation in neurodegenerative diseases
Description Inhibiting misfolded protein propagation in neurodegenerative diseases. Both AD and PD are characterised by the progressive loss of brain cells. Recent evidence suggests that this loss may be due to the release and uptake by brain cells of specific aggregated proteins (misfolded proteins which clump together leading to a progressive spreading of the degeneration). If these processes could be blocked, disease progression could be halted. However, the forces driving these processes are currently poorly understood. Working to change that is the IMPRiND project, which aims to understand how these aggregated proteins are handled once inside brain cells and how they are moved from cell to cell. To do this, the project team will work collaboratively to develop standardised tools and tests to establish disease-relevant mechanisms that could be targeted by drugs in the future.
Objectives 1. Identify disease-relevant misfolded assemblies, imprint their biological properties in vitro and/or in cellulo and generate homogeneous populations in order to assay and interfere with their pathogenic effects. 2. Develop and miniaturise assays to monitor up-take, secretion, 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 high throughput or high content screens. 3. Perform genetic screens based on disease-relevant gene/protein networks and assess druggability of identified targets. 4. 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 models and organotypic cultures or simple model organisms such as Drosophila or zebrafish. 5. Improve existing animal models in order to standardise pathological readouts 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.
Website https://www.imprind.org/
Start date 01-03-2017
End date 28-02-2022
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Name Projects Type of institution Country  
Janssen Pharmaceutica NV EPAD ADAPTED AMYPAD IMPRiND EQIPD NEURONET EMIF IM2PACT PHAGO PRISM RADAR-CNS RADAR-AD ROADMAP IDEA-FAST Pharma-Cog EPND EFPIA Belgium
Eli Lilly And Company Ltd EPAD IMPRiND MOPEAD PHAGO PRISM RADAR-AD ROADMAP NEURONET IDEA-FAST Pharma-Cog EFPIA United Kingdom
AbbVie Ltd IMPRiND EFPIA United Kingdom
H. Lundbeck As EPAD IMPRiND IM2PACT PD-MitoQUANT PHAGO RADAR-CNS ROADMAP Pharma-Cog EFPIA Denmark
Institut De Recherches Servier IMPRiND EMIF EQIPD Pharma-Cog Academia France
Novartis Pharma AG EPAD IMPRiND EQIPD AETIONOMY IM2PACT PRISM RADAR-AD ROADMAP Mobilise-D Pharma-Cog EPND EFPIA Switzerland
Aarhus Universitet IMPRiND IM2PACT ROADMAP EMIF Academia Denmark
Centre National De La Recherche Scientifique CNRS IMPRiND PD-MitoQUANT Pharma-Cog Academia France
Deutsches Zentrum Fur Neurodegenerative Erkrankungen Ev IMPRiND PD-MitoQUANT PHAGO EPND Academia Germany
Idryma Iatroviologikon Ereunon Akademias Athinon IMPRiND Academia Greece
United Kingdom Research And Innovation IMPRiND Academia United Kingdom
Universitaetsmedizin Goettingen - Georg-August-Universitaet Goettingen - Stiftung Oeffentlichen Rechts IMPRiND Academia Germany
Universite De Bordeaux IMPRiND Academia France
University Of Dundee IMPRiND IM2PACT Academia United Kingdom
University Of Cambridge EPAD IMPRiND PHAGO EMIF IDEA-FAST Academia United Kingdom
University Of Oxford EPAD IMPRiND IM2PACT RADAR-AD ROADMAP EMIF EPND Academia United Kingdom
Vib Center for Brain and Disease Research IMPRiND EMIF Academia Belgium
Sciprom SARL IMPRiND SME Switzerland
WP number Description Project  
WP1 Governance and Project Management IMPRiND
WP2 Establish tau and alpha synuclein assays IMPRiND
WP3 Pathway analysis using bioinformatics IMPRiND
WP4 Target validation in advanced models IMPRiND
WP5 Data and Knowledge management IMPRiND
Deliverable number Title Project Submission date Link Keywords  
D5.2 Launch of website, twitter and other dissemination activities IMPRiND 31-05-2017 https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5ba4848e0&appId=PPGMS
D5.1 Press release IMPRiND 31-05-2017 https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5ba485557&appId=PPGMS
D3.7 Consortium Symposium on Pathways and Targets in models of seeded aggregation IMPRiND 31-05-2021 https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5dc5f3bf6&appId=PPGMS
Title First author last name Year Project Link Keywords  
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models Mavroeidi 2019 IMPRiND https://doi.org/10.1007/s00401-019-02014-y Basic science research paper, Multiple system atrophy, Alpha-synuclein, Myelin, Oligodendrocytes, Seeding, Tubulin polymerization promoting protein, animal model
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons Bieri 2019 IMPRiND https://doi.org/10.1007/s00401-019-01995-0 Basic science research paper, clinical research, Parkinson’s disease, Alpha-synuclein, Aggregation, LRRK2, GBA, Genetic interaction
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network Gribaudo 2019 IMPRiND https://doi.org/10.1016/j.stemcr.2018.12.007 Basic science research paper, iPSC, stem cells, Parkinson's disease, microfluidic, prion-like, nucleation, synuclein, Lewy body, human cortical neuron, neuronal dysfunction
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors Shrivastava 2019 IMPRiND https://doi.org/10.15252/embj.201899871 Basic science research paper, clinical research, Alzheimer's disease, neurodegenerative disease, culture models, neurons, tau, membrane
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons Chabrat 2019 IMPRiND https://doi.org/10.1155/2019/2945435 Basic science research paper, stem cells, neurons, disease model, neurodegenerative disease
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration Katsinelos 2019 IMPRiND https://doi.org/10.3389/fimmu.2019.01139 Review article, prion-like proteins, neurodegeneration, tau (MAPT), Fc receptor, microglia, antibody immunity, alpha-synuclein, beta-amyloid
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved Vasili 2019 IMPRiND https://doi.org/10.3389/fnmol.2019.00107 Review article, alpha-synuclein, Parkinson's disease, tau, Alzheimer's disease, spreading
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease Zhang 2018 IMPRiND https://doi.org/10.7554/eLife.43584.001 Basic science research paper, clinical research, Alzheimer's disease, Neurodegenerative disease, tau, microtubule, protein structure
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces Fenyi 2018 IMPRiND https://doi.org/10.1038/s41598-018-28856-2 Basic science research paper, methodology, tau, amyloid, laboratory
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading Kundel 2018 IMPRiND https://doi.org/10.1021/acschemneuro.8b00094 Basic science research paper, Alzheimer's disease, Parkinson's disease, tau, microscopy, filament, assembly
Tau Filaments and the Development of Positron Emission Tomography Tracers. Goedert 2018 IMPRiND https://doi.org/10.3389/fneur.2018.00070 Review article, Alzheimer's disease, Parkinson's disease, tauopathy, tau, filament, PET, diagnosis
Structures of filaments from Pick’s disease reveal a novel tau protein fold Falcon 2018 IMPRiND https://doi.org/10.1038/s41586-018-0454-y Basic science research paper, clinical research, Pick's disease, neurodegenerative disease, Tau, structural biology, cryo-EM
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold Falcon 2018 IMPRiND https://doi.org/10.1007/s00401-018-1914-z Basic science research paper, clinical research, Alzheimer's disease, tau protein, Tauopathy, tau isoform, filamentous tau aggregate, cryo-EM, PET ligand
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein PD cohort Koros 2018 IMPRiND https://doi.org/10.1002/mds.27451 Clinical research paper, Parkinson's disease, alpha‐synuclein, 123I‐FP‐CIT SPECT, caudate nucleus, neuropsychological tests
Neurodegeneration and the ordered assembly of α-synuclein Spillantini 2018 IMPRiND https://doi.org/10.1007/s00441-017-2706-9 Review article, Alpha-synuclein, Multiple system atrophy, Dementia with Lewy bodies, Parkinson’s disease, Ordered assembly
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease Tofaris 2017 IMPRiND https://doi.org/10.3233/JPD-171176 Review article, Parkinson's disease, exosome, Aggregation, alpha-synuclein, biomarker, LRRK2, neurodegeneration
Cryo-EM structures of tau filaments from Alzheimer’s disease Fitzpatrick 2017 IMPRiND https://doi.org/10.1038/nature23002 Basic science research paper, clinical research, Alzheimer's disease, tau filaments, structural biology, cryo-EM, imaging, protein aggregation
How is alpha-synuclein cleared from the cell? Stefanis 2019 IMPRiND https://doi.org/10.1111/jnc.14704 Review article, Parkinson's disease, neurodegenerative disease, Degradation, Exosomes, Lysosomes, Proteasome, alpha‐synuclein, ubiquitin
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy Guerrero-Ferreira 2019 IMPRiND https://doi.org/10.7554/eLife.48907
Novel tau filament fold in corticobasal degeneration Zhang 2020 IMPRiND https://doi.org/10.1038/s41586-020-2043-0 Cryoelectron microscopy, Neurodegeneration
Differential Membrane Binding and Seeding of Distinct α-Synuclein Fibrillar Polymorphs Shrivastava 2020 IMPRiND https://pubmed.ncbi.nlm.nih.gov/32059758/ Basic research paper, protein aggregation, synucleinopathies, alpha-synuclein, Parkinson's disease
Structures of α-synuclein filaments from multiple system atrophy Schweighauser 2020 IMPRiND https://doi.org/10.1038/s41586-020-2317-6 Basic research paper, synucleinopathies, multiple system atrophy, Cryo-EM, protein aggregation
The structural differences between patient-derived α-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies Van der Perren 2020 IMPRiND https://doi.org/10.1007/s00401-020-02157-3 Basic research paper, synucleinopathies, Parkinson's disease, dementia, protein aggregation
Prominent microglial inclusions in transgenic mouse models of α-synucleinopathy that are distinct from neuronal lesions Tanriover 2020 IMPRiND https://doi.org/10.1186/s40478-020-00993-8 Synuclein, Microglia, Inclusion, Prion-like, Amyloid, Conformation, Parkinson’s disease
α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb Rey 2019 IMPRiND https://doi.org/10.1186/s40478-019-0859-3 Alpha-synuclein, Strains, Fibrils, Prion-like spreading, Olfactory bulb
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification Fenyi 2019 IMPRiND https://doi.org/10.1016/j.nbd.2019.05.002 Alpha-synuclein, Parkinson's disease, Protein misfolding, cyclic amplification, Gut, Enteric, nervous system, Biopsy
Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules Falcon 2019 IMPRiND https://doi.org/10.1038/s41586-019-1026-5 Alzheimer's disease, Cryoelectron microscopy, Molecular neuroscience, Neurodegeneration
α‐synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities Alam 2019 IMPRiND https://doi.org/10.1111/jnc.14808 biophysics, conformations, fibrils, oligomers, propagation, synuclein
Distinct alpha‐Synuclein species induced by seeding are selectively cleared by the Lysosome or the Proteasome in neuronally differentiated SH‐SY5Y cells Pantazopoulou 2020 IMPRiND https://doi.org/10.1111/jnc.15174 aggregation, alpha‐synuclein, degradation, lysosome, phosphorylation, proteasome
The expression level of alpha-synuclein in different neuronal populations is the primary determinant of its prion-like seeding Courte 2020 IMPRiND https://doi.org/10.1038/s41598-020-61757-x Mechanisms of disease, Parkinson's disease
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization Dominguez-Meijide 2020 IMPRiND http://dx.doi.org/10.1038/s41598-020-69744-y anle138b, fulvic acid, aSyn, tau, epigallocatechin gallate, dynasore, tau internalization, parkinson, alzheimer
Targeting α-synuclein for PD Therapeutics: A Pursuit on All Fronts Teil 2020 IMPRiND https://doi.org/10.3390/biom10030391 Parkinson’s disease, α-synuclein, aggregation, neurodegeneration, therapy.
Interaction of the chaperones alpha B-crystallin and CHIP with fibrillar alpha-synuclein: Effects on internalization by cells and identification of interacting interfaces Bendifallah 2020 IMPRiND https://doi.org/10.1016/j.bbrc.2020.04.091 Molecular chaperones, Protein-protein interactions, Protein-protein interfaces, Cross-linking, mass spectrometry
Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for PD Fenyi 2021 IMPRiND https://doi.org/10.3390/cells10010139 alpha-synuclein; enteric nervous system; incidental Lewy body disease; Lewy body disease; Parkinson’s disease; protein misfolding cyclic amplification (PMCA); prion-like; synucleinopathy; synuclein strains
Novel self-replicating α-synuclein polymorphs that escape ThT monitoring can spontaneously emerge and acutely spread in neurons De Giorgi 2020 IMPRiND https://doi.org/10.1126/sciadv.abc4364 neurons, amyloid, iso, sample, assay, polymorphs, mouse, fluorescence, nmr,
Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue Miller 2021 IMPRiND https://doi.org/10.1186/s40478-021-01141-6 Prion-like activity, Tau seeded aggregation, Organotypic hippocampal slice cultures, Neurodegeneration, Tauopathies
TNF-α and α-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration Russ 2021 IMPRiND https://doi.org/10.1016/j.celrep.2021.108895 Parkinson’s disease, astrocytes, reactivity, alpha-synuclein, HLA genes, iPSC
Overexpression of α-Synuclein by Oligodendrocytes in Transgenic Mice Does Not Recapitulate the Fibrillar Aggregation Seen in Multiple System Atrophy Laferrière 2020 IMPRiND https://doi.org/10.3390/cells9112371
The differential solvent exposure of N-terminal residues provides ‘fingerprints’ of alpha-synuclein fibrillar polymorphs Landureau 2021 IMPRiND https://doi.org/10.1016/j.jbc.2021.100737 alpha-synuclein, protein misfolding, strains, limited proteolysis, hydrogen-deuterium exchange, mass spectrometry, surface mapping, neurodegenerative disease
Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons Tanudjojo 2021 IMPRiND https://doi.org/10.1038/s41467-021-23682-z neurons, aggregation, fibrils, brain, amplification, patients, aggregates
Identification of cis-acting determinants mediating the unconventional secretion of tau Katsinelos 2021 IMPRiND https://doi.org/10.1038/s41598-021-92433-3 Alzheimer's disease, Protein transport, Secretion
LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies Emmenegger 2021 IMPRiND https://doi.org/10.15252/emmm.202114745 cells, lag3, antibodies, neurons, mice, expression, cell, brain, clinical
Structure-based classification of tauopathies Shi 2021 IMPRiND https://doi.org/10.1038/s41586-021-03911-7 Cryoelectron microscopy, Neurodegeneration, Taupathy, progressive supranuclear palsy, filaments
Microglial inclusions and neurofilament light chain release follow neuronal α-synuclein lesions in long-term brain slice cultures Barth 2021 IMPRiND https://doi.org/10.1186/s13024-021-00471-2 Alpha-synuclein, Microglia, Neurofilament light chain, Slice culture
CSF p-tau increase in response to Aβ-type and Danish-type cerebral amyloidosis and in the absence of neurofibrillary tangles Kaeser 2021 IMPRiND https://doi.org/10.1007/s00401-021-02400-5 mice, csf, tau, amyloid, biomarkers
Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells Vasili 2022 IMPRiND https://doi.org/10.1007/s12035-021-02713-2 PD, LBs, aSyn, Aggregation, Phosphorylation
Initiation and progression of α-synuclein pathology in Parkinson’s disease Tofaris 2022 IMPRiND https://doi.org/10.1007/s00018-022-04240-2 Neurodegeneration, Fibril, Oligomers, Strains, Lewy body, Propagation
Title Description Type Project  
Genetic screens for tau and alpha-synuclein aggregation

IMPRiND has performed genetic screens to identify modifiers of alpha-synuclein and tau aggregation. These include both focused and genome-wide screens. Data will become available upon completion of the analysis and deposition to open access repositories. For more information please visit:

https://www.imprind.org/contact/

 dataset-non-clinical-imprind-4 IMPRiND
iPSC-based and organotypic cultures, neuronal models and animal models of alpha-synuclein or tau aggregation or propagation

IMPRiND has developed a number of models to investigate fibril-induced alpha-synuclein or tau aggregation in primary or iPSC-derived neurons and propagation of aggregates in organotypic cultures and animal models. For more information, please see:

https://link.springer.com/article/10.1007/s00401-019-01995-0

https://link.springer.com/article/10.1007/s00401-019-02014-y

 disease-model-non-clinical-imprind-5 IMPRiND
Tools for isolating and characterising Tau & a-Synuclein, including aggregation assays

IMPRiND has optimised protocols for the isolation and characterisation of proteopathic assemblies for tau and alpha-synuclein as well as assays to measure aggregation that are suitable for screening or target validation. For more infromation, please see:

https://doi.org/10.1038/nature23002

https://doi.org/10.1007/s00401-018-1914-z

https://doi.org/10.15252/embj.201899871

https://doi.org/10.1016/j.stemcr.2018.12.007

 tools-non-clinical-imprind-14 IMPRiND
Website: https://www.imprind.org/

 

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