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Neuronal nicotinic acetylcholine receptors from genes to diseases

English title Neuronal nicotinic acetylcholine receptors from genes to diseases
Applicant Bertrand Daniel
Number 101787
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2003 - 30.09.2010
Approved amount 841'166.00
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Keywords (5)

nicotinic acetylcholine receptors; neurotransmission; epilepsy; structure function; retina

Lay Summary (English)

Lead
Lay summary
It is during the second half of the sixteen century that the French gentlemen Jean Nicot introduced to the queen mother Catherine de Medici the usage of a plant extract for her headache. This plant immediately became a success and was called after him as Nicotania. Better known as tobacco this plant produces a natural alkaloid termed nicotine, which has been shown to be a powerful agonist at the neuromuscular junction receptors that were then called nicotinic acetylcholine receptors.Although it is known since more than four hundred years that nicotine causes multiple effects on the peripheral and central nervous system our understanding of its properties remained limited because the nicotine site of action was not identified. The advance of cloning and sequencing allowed the identification of an entire family of genes encoding nicotinic acetylcholine receptors that are expressed by neurons and nonneuronal cells.
These progresses marked a new step in neuroscience and numerous studies have since then illustrated the importance of neuronal nicotinic acetylcholine receptors in brain function. Experiments carried out using reconstituted receptors allowed to characterize the physiological and pharmacological properties of the different receptor subtypes and to resolve at the molecular level the contribution of single amino acid residues. In parallel, genetic studies have shown that polymorphisms in the gene sequences observed in the population can be at the origin of individual physiological and pharmacological differences. For example the discovery of a mutation in CHRNA4, the gene encoding for the a4 subunit of the neuronal nicotinic acetylcholine receptors, and the association of this variant with a form of nocturnal epilepsy further highlighted the importance of these receptors in brain dysfunction. In view of the natural variation of receptor properties it can be foreseen that polymorphisms of the genes encoding for the neuronal nicotinic acetylcholine receptors may account for the increased nicotine dependence in some individuals.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
53638 Human and mammalian neuronal nicotinic acetylcholine receptors: their structure-function relationships and allosteric modulations 01.10.1998 Project funding (Div. I-III)

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