Latest news

Collection of research highlights now available

A collection of all IMPRiND research highlights is now available for download. This document is a journey through the research ...

New publication in Acta Neuropathologica

Elevation of p-Tau in CSF is linked to the aggregation of amyloidogenic proteins rather than a unique feature of β-amyloidosis and can ...

Publication in Nature by the LMB team

The paper on "Structure-based classification of Tauopathies", by Michel Goedert and his colleagues at LMB, is now online at @nature. To ...

Blocking aggregate propagation in neurodegenerative diseases


Blocking aggregate propagation in neurodegenerative diseases IMPRiND – Inhibiting Misfolded protein Propagation In Neurodegenerative Diseases – is an international consortium that aims to map and target critical steps in the propagation of misfolded tau and α-synuclein, considered the main culprits of neurodegeneration in Alzheimer's and Parkinson's disease respectively. Our plans are built upon:
  • 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.
  • 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.
  • Perform genetic screens based on disease-relevant gene/protein networks and assess druggability of identified targets.
  • 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.
  • 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.
In the IMPRiND consortium, we will construct this entire pipeline to examine the propagation of α-synuclein and tau and test their tractability against disease progression.
IMPRIND started in March 2017 and will run until February 2021.

Most recent publications

1.
Tau in the brain interstitial fluid is fragmented and seeding–competent.
Neurobiology of Aging 109, 64–77 (2022). doi: 10.1016/j.neurobiolaging.2021.09.013
2.
Similar neuronal imprint and no cross-seeded fibrils in α-synuclein aggregates from MSA and Parkinson’s disease.
npj Parkinson’s Disease 8, 10 (2022). doi: 10.1038/s41531-021-00264-w. Archive: PMC
3.
Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells.
Molecular Neurobiology 59, 1273–1284 (2022). doi: 10.1007/s12035-021-02713-2
1.
Tau in the brain interstitial fluid is fragmented and seeding–competent.
Neurobiology of Aging 109, 64–77 (2022). doi: 10.1016/j.neurobiolaging.2021.09.013
2.
Similar neuronal imprint and no cross-seeded fibrils in α-synuclein aggregates from MSA and Parkinson’s disease.
npj Parkinson’s Disease 8, 10 (2022). doi: 10.1038/s41531-021-00264-w. Archive: PMC
3.
Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells.
Molecular Neurobiology 59, 1273–1284 (2022). doi: 10.1007/s12035-021-02713-2
1.
Tau in the brain interstitial fluid is fragmented and seeding–competent.
Neurobiology of Aging 109, 64–77 (2022). doi: 10.1016/j.neurobiolaging.2021.09.013
2.
Similar neuronal imprint and no cross-seeded fibrils in α-synuclein aggregates from MSA and Parkinson’s disease.
npj Parkinson’s Disease 8, 10 (2022). doi: 10.1038/s41531-021-00264-w. Archive: PMC
3.
Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells.
Molecular Neurobiology 59, 1273–1284 (2022). doi: 10.1007/s12035-021-02713-2

Latest news

New publication in Acta Neuropathologica

Elevation of p-Tau in CSF is linked to the aggregation of amyloidogenic proteins rather than a unique feature of β-amyloidosis and can ...

Publication in Nature by the LMB team

The paper on "Structure-based classification of Tauopathies", by Michel Goedert and his colleagues at LMB, is now online at @nature. To ...

This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 116060. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 17.00038.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.

© 2019 IMPRiND Project – created by SCIPROMPrivacy policy