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Gating mechanism and pharmacological modulation of nicotinic acetylcholine receptors

Objective

Pentameric ligand-gated ion channels (pLGICs), including nicotinic acetylcholine, 5HT3, glycine, and GABAA receptors, are membrane proteins specialized in the communication between neurons. These neurotransmitter receptors are the target of general anaesthetics, anxiolytics, alcohols and nicotine. In particular, enhancing the activity of neuronal nicotinic receptors holds promises in the treatment of pathologies including nicotine addiction, schizophrenia and Alzheimer’s disease. The current project aims at deciphering the molecular and pharmacological determinants of positive allosteric modulators of neuronal nicotinic receptors. We will over-express and purify these proteins, study their pharmacology through electrophysiology in cell lines and planar lipid bilayer, and surface plasmon resonance binding studies. Our study will provide insights into the molecular mechanisms of allosteric regulation, paving the way for the rational design of allosteric modulators with therapeutic potential.

Coordinator

INSTITUT PASTEUR
Net EU contribution
€ 185 076,00
Address
RUE DU DOCTEUR ROUX 25-28
75724 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 185 076,00