Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurosci
2009 Jan 28;294:918-29. doi: 10.1523/JNEUROSCI.3952-08.2009.
Show Gene links
Show Anatomy links
A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides.
Liu Q
,
Huang Y
,
Xue F
,
Simard A
,
DeChon J
,
Li G
,
Zhang J
,
Lucero L
,
Wang M
,
Sierks M
,
Hu G
,
Chang Y
,
Lukas RJ
,
Wu J
.
???displayArticle.abstract???
Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies.
Azam,
Co-expression of alpha7 and beta2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons.
2003, Pubmed
Azam,
Co-expression of alpha7 and beta2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons.
2003,
Pubmed
Burghaus,
Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients.
2000,
Pubmed
Counts,
Alpha7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease.
2007,
Pubmed
Dineley,
Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins.
2002,
Pubmed
Dineley,
beta -Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors expressed in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Dolezal,
Beta-amyloid and cholinergic neurons.
2003,
Pubmed
Dougherty,
Beta-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex.
2003,
Pubmed
El-Hajj,
Pharmacological and immunological identification of native alpha7 nicotinic receptors: evidence for homomeric and heteromeric alpha7 receptors.
2007,
Pubmed
Flores,
A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment.
1992,
Pubmed
Fu,
Beta-amyloid peptide activates non-alpha7 nicotinic acetylcholine receptors in rat basal forebrain neurons.
2003,
Pubmed
Geerts,
Indicators of neuroprotection with galantamine.
2005,
Pubmed
Gopalakrishnan,
Stable expression, pharmacologic properties and regulation of the human neuronal nicotinic acetylcholine alpha 4 beta 2 receptor.
1996,
Pubmed
Grassi,
Amyloid beta(1-42) peptide alters the gating of human and mouse alpha-bungarotoxin-sensitive nicotinic receptors.
2003,
Pubmed
,
Xenbase
Haass,
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
2007,
Pubmed
Henderson,
Somato-dendritic nicotinic receptor responses recorded in vitro from the medial septal diagonal band complex of the rodent.
2005,
Pubmed
Horn,
Muscarinic activation of ionic currents measured by a new whole-cell recording method.
1988,
Pubmed
Jensen,
Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations.
2005,
Pubmed
Khiroug,
Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels.
2002,
Pubmed
,
Xenbase
Kuo,
Elevated abeta42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AbetaPP metabolism.
2000,
Pubmed
Lahiri,
Nicotine reduces the secretion of Alzheimer's beta-amyloid precursor protein containing beta-amyloid peptide in the rat without altering synaptic proteins.
2002,
Pubmed
Lamb,
Inhibition of neuronal nicotinic acetylcholine receptor channels expressed in Xenopus oocytes by beta-amyloid1-42 peptide.
2005,
Pubmed
,
Xenbase
Levin,
Nicotinic treatment for cognitive dysfunction.
2002,
Pubmed
Lindstrom,
Neuronal nicotinic acetylcholine receptors.
1996,
Pubmed
Lindstrom,
Structure and function of neuronal nicotinic acetylcholine receptors.
1996,
Pubmed
Liu,
Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model.
2007,
Pubmed
Liu,
beta -Amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons.
2001,
Pubmed
Liu,
Role of endogenous nicotinic signaling in guiding neuronal development.
2007,
Pubmed
Lukas,
International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits.
1999,
Pubmed
Mansvelder,
Nicotinic modulation of neuronal networks: from receptors to cognition.
2006,
Pubmed
Mehta,
Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease.
2000,
Pubmed
Moser,
Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures.
2007,
Pubmed
Mudo,
Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms.
2007,
Pubmed
Nagele,
Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer's disease.
2002,
Pubmed
Nordberg,
Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications.
2001,
Pubmed
Pettit,
beta-Amyloid(1-42) peptide directly modulates nicotinic receptors in the rat hippocampal slice.
2001,
Pubmed
Pym,
Subtype-specific actions of beta-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (alpha7, alpha4beta2, alpha3beta4) expressed in Xenopus laevis oocytes.
2005,
Pubmed
,
Xenbase
Sadot,
Activation of m1 muscarinic acetylcholine receptor regulates tau phosphorylation in transfected PC12 cells.
1996,
Pubmed
Saragoza,
Identification of an alternatively processed nicotinic receptor alpha7 subunit RNA in mouse brain.
2003,
Pubmed
Selkoe,
Translating cell biology into therapeutic advances in Alzheimer's disease.
1999,
Pubmed
Severance,
The alpha7 nicotinic acetylcholine receptor subunit exists in two isoforms that contribute to functional ligand-gated ion channels.
2004,
Pubmed
,
Xenbase
Severance,
Distribution and synaptic localization of nicotinic acetylcholine receptors containing a novel alpha7 subunit isoform in embryonic rat cortical neurons.
2004,
Pubmed
Sivaprakasam,
Towards a unifying hypothesis of Alzheimer's disease: cholinergic system linked to plaques, tangles and neuroinflammation.
2006,
Pubmed
Thinschmidt,
Medial septal/diagonal band cells express multiple functional nicotinic receptor subtypes that are correlated with firing frequency.
2005,
Pubmed
Wang,
beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology.
2000,
Pubmed
Whiting,
Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptors.
,
Pubmed
Wu,
Electrophysiological, pharmacological, and molecular evidence for alpha7-nicotinic acetylcholine receptors in rat midbrain dopamine neurons.
2004,
Pubmed
Wu,
1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons.
2002,
Pubmed
Wu,
beta-Amyloid directly inhibits human alpha4beta2-nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells.
2004,
Pubmed
Yan,
Alzheimer's disease: interactions between cholinergic functions and beta-amyloid.
2004,
Pubmed
Yu,
Functional contribution of the alpha5 subunit to neuronal nicotinic channels expressed by chick sympathetic ganglion neurones.
1998,
Pubmed
