Team Guillaume LEBON – Cyril GOUDET
Molecular and Structural Mechanisms of Neuromodulation
Project Physiopathologic function and therapeutic potential of GPCR in nervous system diseases
PRINCIPAL INVESTIGATOR
IGF staff involved
Fanny MALHAIRE
IE CNRS
Iona TRUONG
PhD Student Inserm
Guillaume LEBON
CRCN CNRS
In recent years, our research has focused on the pathophysiological function and therapeutic potential of neuromodulation systems associated with metabotropic glutamate or adenosine receptors. To better study and understand their roles, we use photopharmacology in particular, which uses light to control endogenous brain receptors with great spatiotemporal precision. Among the various pathologies of the nervous system, we pay particular attention to chronic pain and more recently to other pathologies such as Alzheimer’s disease and autistic spectrum syndromes.
Chronic pain
Unlike acute pain, chronic pain does not serve as a physiological alarm signal and should be considered as an illness in its own right. It is a common problem affecting around 20% of the European population. Unfortunately, current drugs have limited effectiveness: only half of patients suffering from chronic pain are adequately relieved. In addition, these treatments are often associated with undesirable side effects, such as respiratory depression and addiction to conventional analgesics targeting µ-opioid receptors. There is therefore a considerable unmet need for new analgesics to treat chronic pain. A better understanding of the neuronal and molecular pathophysiological mechanisms involved in the regulation of chronic pain is essential in order to identify new pharmacological targets for the treatment of pain. In this context, our work focuses on the roles of metabotropic glutamate receptors and adenosine receptors, which are neuromediators strongly involved in pain signalling, and their therapeutic potential.
Photopharmacological manipulation of amygdala metabotropic glutamate receptor mGlu4 alleviates neuropathic pain. Pereira et al. Pharmacological Research. 2023. https://doi.org/10.1016/j.phrs.2022.106602
Main publications
• Notartomaso S. et al (2024) bioRxiv. Jan 3:2024.01.02.573945
• Pereira, V. et al. (2023) Pharmacol Res 187, 106602
• Pereira, V. & Goudet, C. (2019) Front Mol Neurosci 11
• Zussy, C. et al. (2018) Mol Psychiatry 23, 509-520
• Font, J. et al. (2017) eLife 6
• Vilar, B. et al. (2013) J Neurosci 33, 18951-18965
Funding
• 2018-2020 PICS CNRS NEUROPHOTOPHARMACOLOGY – Coordinateur
• 2017-2020 ANR2016 EXPLORER – Coordinateur
• 2013-2016 ANR2013 ANTARES – Coordinateur
• 2013-2016 Neuron eranet LIGHTPAIN – Partenaire
Collaborations
• Jérôme Busseroles (Clermont-Ferrand)
• Éric Lingueglia (Nice)
• Ferdinando Nicoletti (Rome)
• Francesco Ciruela (Barcelona)
Alumni
• Juri Aparicio Arias (IE)
• Vanessa Pereira (Postdoc)
• Charleine Zussy (Postdoc)
• Bruno Vilar (Thèse)
• Lucie Maujean (stage BUT)
Other nervous system pathologies
In collaboration with teams specialized in these pathologies, we have more recently been focusing on the role of metabotropic glutamate receptors and the therapeutic potential of photopharmacology in Alzheimer’s disease (collab. L. Givalois) and autism spectrum disorders (collab. J. Le Merrer & J. Becker).
Funding
• 2021-2024 FRM MND2020 OPA – Collaborateur
• 2020-2024 MUSE Univ Montpellier GAIA – Collaborateur
• 2018-2023 Neuron eranet MAGNOLIA – Coordinateur
Collaborations
• Julie Le Merrer (Tours)
• Jerome Becker (Tours)
• Laurent Givalois (Montpellier)
Alumni
• Anaelle Dumazer (thèse)
• Juri Aparicio Arias (IE)
• Julie Corre (postdoc)
• Oceane Vigne (stage BUT)
