title: Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment.
abstract: Alzheimer's Disease (AD) is the major form of senile dementia, characterized by neuronal loss, extracellular deposits, and neurofibrillary tangles. It is accompanied by a loss of cholinergic tone, and acetylcholine (ACh) levels in the brain, which were hypothesized to be responsible for the cognitive decline observed in AD. Current medication is restricted to enhancing cholinergic signalling for symptomatic treatment of AD patients. The nicotinic acetylcholine receptor family (nAChR) and the muscarinic acetylcholine receptor family (mAChR) are the target of ACh in the brain. Both families of receptors are affected in AD. It was demonstrated that amyloid beta (Aβ) interacts with nAChRs. Here we discuss how Aβ activates or inhibits nAChRs, and how this interaction contributes to AD pathology. We will discuss the potential role of nAChRs as therapeutic targets. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.
authors.affiliation: Département de Neuroscience, Institut Pasteur, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Paris Cedex 15, France; CNRS, UMR 3571, Paris, France. Electronic address: sylvia.lombardo@pasteur.fr.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Lombardo
authors.affiliation: Département de Neuroscience, Institut Pasteur, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Paris Cedex 15, France; CNRS, UMR 3571, Paris, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Maskos
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018722:Nicotinic Agonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: Alzheimer's disease; Aβ peptide; Cholinergic system; Nicotine; Nicotinic receptor