Research subject

Our research team aims to understand the molecular and cellular mechanisms responsible for the brain degeneration in proteinopathies and (ii) the subsequent symptoms in these same diseases. Three proteins receive our attention: alpha-synuclein, Tau and TDP-43.

Our research is developed around different axes:

  • Biophysics of amyloid polymorphs.

This axis proposes to study the structure-activity relationship of amyloids using numerous biochemical and biophysical tools applied to synthetic assemblies and brain extracts from patients, but also based on in vitro models based on primary neuronal and glial cultures. These analytical and functional approaches aim at deciphering the cascade of events linking amyloid aggregation to neurodegeneration and at identifying molecular targets for the development of neuroprotective approaches.

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  • Modeling proteinopathies

This line of research, conducted in vivo, will allow us to study (i) the mechanistic of the induced degeneration and (ii) the pathophysiological consequences (behaviour, electrophysiology, neurochemistry, anatomo-pathology) through the administration of aggregated proteins in rodents and non-human primates. The specific role of the extra-cellular space in the propagation of aggregative information is particularly highlighted.

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  • Physiopathology of autophagic dysfunctions

These proteinopathies are all accompanied by autophagy dysfunctions (autophagic lysosomal pathway, macroautophagy, mitophagy, chaperone-mediated autophagy). Based on pathophysiological investigations, this axis aims to develop innovative therapeutic approaches (nanotechnology, gene therapy) for these different pathways in proteinopathies.

2023_T01_Fig04

  • Therapeutics for disease symptoms

Our history includes, in collaboration with the Centre Hospitalier Régional Universitaire de Bordeaux, a translational approach in the field of neurodegenerative diseases oriented towards disease management and medical applications. We aim to identify new therapeutic targets for specific symptoms through pathophysiological studies in experimental models and humans.

 

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Latest publications

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Criteria : Author : "Bezard", Laboratoire(Affiliation) : "UMR5293", Publication type : "('ART')"
Number of occurrences founded : 202.

titre
Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates
auteur
Morgane Darricau, Taxiarchis Katsinelos, Flavio Raschella, Tomislav Milekovic, Louis Crochemore, Qin Li, Grégoire Courtine, William Mcewan, Benjamin Dehay, Erwan Bezard, Vincent Planche
article
Brain - A Journal of Neurology , 2022, pp.awac428. ⟨10.1093/brain/awac428⟩
identifiant
inserm-03891736
titre
The Zinc Ionophore Clioquinol Reduces Parkinson’s Disease Patient-Derived Brain Extracts-Induced Neurodegeneration
auteur
Margaux Teil, Evelyne Doudnikoff, Marie-Laure Thiolat, Sylvain Bohic, Erwan Bezard, Benjamin Dehay
article
Molecular Neurobiology, 2022, Online ahead of print. ⟨10.1007/s12035-022-02974-5⟩
identifiant
inserm-03773965
titre
Acidic nanoparticles protect against α‐synuclein‐induced neurodegeneration through the restoration of lysosomal function
auteur
Marie‐laure Arotcarena, Federico Soria, Anthony Cunha, Evelyne Doudnikoff, Geoffrey Prévot, Jonathan Daniel, Mireille Blanchard‐desce, Philippe Barthélémy, Erwan Bezard, Sylvie Crauste‐manciet, Benjamin Dehay
article
Aging Cell, 2022, pp.e13584. ⟨10.1111/acel.13584⟩
identifiant
inserm-03617988
titre
Brain injections of glial cytoplasmic inclusions induce a multiple system atrophy-like pathology
auteur
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Michele Morari, Wassilios Meissner, María Trinidad Herrero, Miquel Vila, Jose Obeso, Erwan Bezard, Benjamin Dehay
article
Brain - A Journal of Neurology , 2022, Online ahead of print. ⟨10.1093/brain/awab374⟩
identifiant
inserm-03609490
titre
Neurons with Cat’s Eyes: A Synthetic Strain of α-Synuclein Fibrils Seeding Neuronal Intranuclear Inclusions
auteur
Francesca de Giorgi, Muhammed Bilal Abdul-Shukkoor, Marianna Kashyrina, Leslie-Ann Largitte, Francesco de Nuccio, Brice Kauffmann, Alons Lends, Florent Laferrière, Sébastien Bonhommeau, Dario Domenico Lofrumento, Luc Bousset, Erwan Bezard, Thierry Buffeteau, Antoine Loquet, Francois Ichas
article
Biomolecules, 2022, 12 (3), pp.436. ⟨10.3390/biom12030436⟩
identifiant
hal-03628777