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Gating mechanism and pharmacological modulation of nicotinic acetylcholine receptors

Objectif

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.

Mots‑clés

Coordinateur

INSTITUT PASTEUR
Contribution nette de l'UE
€ 185 076,00
Adresse
RUE DU DOCTEUR ROUX 25-28
75724 Paris
France

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Région
Ile-de-France Ile-de-France Paris
Type d’activité
Research Organisations
Liens
Coût total
€ 185 076,00