Research subject

Our goal is to understand molecular and cellular mechanisms responsible for motor and non-motor symptoms in Parkinson’s disease and atypical parkinsonism as well as the disturbed response to L-dopa. Our goal is thus to identify novel therapeutic targets on the ground of pathophysiological studies in experimental models (ranging from cell culture to non-human primate) as well as in man.

The cell death mechanisms and the pathological response to dopamine replacement therapies in parkinsonian syndromes are at the center of our research work. I close connection with the University Hospital of Bordeaux, we develop a translational research in the field of neurodegenerative disorders, oriented towards disease management and medical applications.

The research activities of the team evolve around the following axes :

  • Mechanisms of cell death in parkinsonian syndromes

Parkinson’s disease is characterized by a progressive accumulation and propagation of a-synuclein likely responsible for their subsequent death. Our objective is to understand these mechanisms for then proposing adapted therapeutic approaches.

  • Decrypting brain pathophysiology using innovative optical nanoprobes

Understanding the role of the extracellular space (ECS) in modulating neuronal communication represents a knowledge frontier in current brain research. We aim to decrypt the intimate interplay between extracellular space and receptors in shaping neuronal network (dys)function. To reach our goal we use innovative multidisciplinary approaches based on new optical nanoimaging reporters and tailored methodologies for manipulating brain functions in state-of-the-art Alzheimer’s disease and Parkinson’s disease models.

  • Pathophysiology of L-dopa-induced dyskinesia

Our 15 years of work now culminate with a series of clinical trials testing the efficacy of pharmacological and non-pharmacological approaches upon dyskinesia severity.

  • Purinergic signalling in the central nervous system

Our overall goal is to better understand the regulation and function of ATP signaling in the central nervous system. We will determine the spatiotemporal profile of ATP actions as well as the profile of expression of purine receptor during both neurogenesis and in pathological states.

Research axes

  • Modelling prion-like dissemination of synucleinopathies and tauopathies in nervous system in Parkinsonian syndromes and dementias.
  • Study of targeting autophagy as a potential cure of Parkinson’s disease.
  • Study of key mechanisms contributing to α-synuclein accumulation to counteract Parkinson’s disease and Multiple System Atrophy progression.
  • Improvement of transgenesis approaches in neurodegenerative diseases modelling.
  • Study of the role of extracellular space in neuronal communication.

 

Complete bibliography >>>

Latest publications

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Criteria : Author : "Bezard", Laboratoire(Affiliation) : "UMR5293", Publication type : "('ART')"
Number of occurrences founded : 190.

titre
Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
auteur
Federico Soria, Chiara Paviolo, Evelyne Doudnikoff, Marie-Laure Arotcarena, Antony Lee, Noémie Danné, Amit Kumar Mandal, Philippe Gosset, Benjamin Dehay, Laurent Groc, Laurent Cognet, Erwan Bézard
article
Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.3440. ⟨10.1038/s41467-020-17328-9⟩
identifiant
inserm-02904850
titre
Evidence for the spread of human-derived mutant huntingtin protein in mice and non-human primates
auteur
Philippe Gosset, Alexander Maxan, Melanie Alpaugh, Ludivine Breger, Benjamin Dehay, Zhu Tao, Zhang Ling, Chuan Qin, Giulia Cisbani, Nadia Fortin, Jean-Paul Vonsattel, Steve Lacroix, Abid Oueslati, Erwan Bezard, Francesca Cicchetti
article
Neurobiology of Disease, Elsevier, 2020, 141, pp.104941. ⟨10.1016/j.nbd.2020.104941⟩
identifiant
inserm-02613508
titre
Identification of distinct pathological signatures induced by patient-derived $α$-synuclein structures in nonhuman primates
auteur
Mathieu Bourdenx, Aurélien Nioche, Sandra Dovero, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Nicolas P. Rougier, Alice Prigent, Philippe Aubert, Sylvain Bohic, Christophe Sandt, Florent Laferrière, Evelyne Doudnikoff, Niels Kruse, Brit Mollenhauer, Salvatore Novello, Michele Morari, Thierry Leste-Lasserre, Ines Trigo Damas, Michel Goillandeau, Celine Perier, Cristina Estrada, Nuria García Carrillo, Ariadna Recasens, Nishant Narayanan Vaikath, Omar El Agnaf, Maria Trinidad Herrero, Pascal Derkinderen, Miquel Vila, Jose A Obeso, Benjamin Dehay, Erwan Bezard
article
Science Advances , American Association for the Advancement of Science (AAAS), 2020, 6 (20), pp.eaaz9165. ⟨10.1126/sciadv.aaz9165⟩
identifiant
hal-02611441
titre
Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates
auteur
Marie-Laure Arotcarena, Sandra Dovero, Alice Prigent, Mathieu Bourdenx, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Maddalena Tasselli, Philippe Aubert, Niels Kruse, Brit Mollenhauer, Ines Trigo Damas, Cristina Estrada, Nuria Garcia-Carrillo, Nishant Vaikath, Omar El-Agnaf, Maria Trinidad Herrero, Miquel Vila, José Obeso, Pascal Derkinderen, Benjamin Dehay, Erwan Bezard
article
Brain - A Journal of Neurology , Oxford University Press (OUP), 2020, pp.awaa096. ⟨10.1093/brain/awaa096⟩
identifiant
inserm-02613509
titre
Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates
auteur
Alexander Maxan, Giacomo Sciacca, Melanie Alpaugh, Zhu Tao, Ludivine Breger, Benjamin Dehay, Zhang Ling, Chuan Qin, Giulia Cisbani, Maria Masnata, Shireen Salem, Steve Lacroix, Abid Oueslati, Erwan Bezard, Francesca Cicchetti
article
Neurobiology of Disease, Elsevier, 2020, pp.104951. ⟨10.1016/j.nbd.2020.104951⟩
identifiant
inserm-02615641