Abstract
Alzheimer's disease (AD) is the most common form of brain dementia characterized by the accumulation of β-amyloid peptides (Aβ) and loss of forebrain cholinergic neurons. Aβ accumulation and aggregation are thought to contribute to cholinergic neuronal degeneration, in turn causing learning and memory deficits, but the specific targets that mediate Aβ neurotoxicity remain elusive. Recently, accumulating lines of evidence have demonstrated that Aβ directly modulates the function of neuronal nicotinic acetylcholine receptors (nAChRs), which leads to the new hypothesis that neuronal nAChRs may serve as important targets that mediate Aβ neurotoxicity. In this review, we summarize current studies performed in our laboratory and in others to address the question of how Aβ modulates neuronal nAChRs, especially nAChR subunit function.
Similar content being viewed by others
Article PDF
References
Coyle JT, Price DL, DeLong MR . Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 1983; 219: 1184–90.
Aubert I, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R . Comparative alterations of nicotinic and muscarinic bindingsites in Alzheimer's and Parkinson's diseases. J Neurochem 1992; 58: 529–41.
Selkoe DJ . Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid β-protein. J Alzheimers Dis 2001; 3: 75–80.
Marin DB, Sewell MC, Schlechter A . Alzheimer's disease. Accurate and early diagnosis in the primary care setting. Geriatrics 2002; 57: 36–40; quiz 43.
Auld DS, Kornecook TJ, Bastianetto S, Quirion R . Alzheimer's disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002; 68: 209–45.
Dolezal V, Kasparova J . β-amyloid and cholinergic neurons. Neurochem Res 2003; 28: 499–506.
Levin ED, Simon BB . Nicotinic acetylcholine involvement incognitive function in animals. Psychopharmacology (Berl) 1998; 138: 217–30.
Newhouse PA, Kelton M . Clinical aspects of nicotinic agents: therapeutic applications in central nervous system disorders. In Clementi F, Gotti C, Fornasari D, editors. Handbook of experimental pharmacology: neuronal nicotinic receptors. Heidelberg: Springer; 1999. p 779–812.
Pettit DL, Shao Z, Yakel JL . β-Amyloid (1–42) peptide directlymodulates nicotinic receptors in the rat hippocampal slice. J Neurosci 2001; 21: RC120.
Liu Q, Kawai H, Berg DK . β-Amyloid peptide blocks theresponse of α7-containing nicotinic receptors on hippocampalneurons. Proc Natl Acad Sci USA 2001; 98: 4734–9.
Dineley KT, Bell KA, Bui D, Sweatt JD . β-Amyloid peptideactivates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Biol Chem 2002; 277: 25056–61.
Lamb PW, Melton MA, Yakel JL . Inhibition of neuronal nicotinic acetylcholine receptor channels expressed in Xenopus oocytes by β-amyloid1–42 peptide. J Mol Neurosci 2005; 27: 13–21.
Pym L, Kemp M, Raymond-Delpech V, Buckingham S, Boyd CA, Sattelle D . Subtype-specific actions of β-amyloid peptideson recombinant human neuronal nicotinic acetylcholine receptors (α7, α4α2, α3α4) expressed in Xenopus laevis oocytes. Br J Pharmacol 2005; 146: 964–71.
Hernandez CM, Terry AV Jr . Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor. Neuroscience 2005; 130: 997–1012.
Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R, et al. Chronic nicotine treatment reduces β-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). J Neurochem 2002; 81: 655–8.
White HK, Levin ED . Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Psychopharmacology (Berl) 1999; 143: 158–65.
Seo J, Kim S, Kim H, Park CH, Jeong S, Lee J, et al. Effects of nicotine on APP secretion and Aβ- or CT(105)-induced toxicity. Biol Psychiatry 2001; 49: 240–7.
Lindstrom J, Anand R, Gerzanich V, Peng X, Wang F, Wells G . Structure and function of neuronal nicotinic acetylcholine receptors. Prog Brain Res 1996; 109: 125–37.
Albuquerque EX, Alkondon M, Pereira EF, Castro NG, Schrattenholz A, Barbosa CT, et al. Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function. J Pharmacol Exp Ther 1997; 280: 1117–36.
Lukas RJ, Changeux JP, Le Novère N, Albuquerque EX, Balfour DJK, Berg DK, et al. International Union of Pharmacology, current status of the nomenclature for nicotinic acetylcholinereceptors and their subunits. Pharmacol Rev 1999; 51: 397–401.
Dajas-Bailador F, Wonnacott S . Nicotinic acetylcholine receptors and the regulation of neuronal signalling. Trends Pharmacol Sci 2004; 25: 317–24.
Clementi F, Fornasari D, Gotti C . Neuronal nicotinic receptors, important new players in brain function. Eur J Pharmacol 2000; 393: 3–10.
Jensen AA, Frolund B, Liljefors T, Krogsgaard-Larsen P . Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem 2005; 48: 4705–45.
Lukas RJ . Pharmacological effects of nicotine and nicotinic receptor subtype pharmacological profiles. In: George TP, editor. Medication treatments for nicotine dependence. Boca Raton: CRC Press; 2006. p 7–44.
Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, et al. Acetylcholine receptors containing the α2 subunit are involved in the reinforcing properties of nicotine. Nature 1998; 391: 173–7.
Klink R, de Kerchove, D'Exaerde A, Zoli M, Changeux JP . Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci 2001; 21: 1452–63.
Champtiaux N, Changeux JP . Knockout and knockin mice to investigate the role of nicotinic receptors in the central nervoussystem. Prog Brain Res 2004; 145: 235–51.
Marubio LM, Gardier AM, Durier S, David D, Klink R, Arroyo-Jimenez MM, et al. Effects of nicotine in the dopaminergic system of mice lacking the α4 subunit of neuronal nicotinic acetylcholine receptors. Eur J Neurosci 2003; 17: 1329–37.
Tapper AR, McKinney SL, Nashmi R, Schwarz J, Deshpande P, Labarca C, et al. Nicotine activation of α4* receptors: sufficient for reward, tolerance, and sensitization. Science 2004; 306: 1029–32.
Salminen O, Murphy KL, McIntosh JM, Drago J, Marks MJ, Collins AC, et al. Subunit composition and pharmacology of two classes of striatal presynaptic nicotinic acetylcholine receptors mediating dopamine release in mice. Mol Pharmacol 2004; 65: 1526–35.
McGehee DS, Role LW . Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol 1995; 57: 521–46.
Alkondon M, Pereira EF, Barbosa CT, Albuquerque EX . Neuronal nicotinic acetylcholine receptor activation modulates gamma-aminobutyric acid release from CA1 neurons of rat hippocampal slices. J Pharmacol Exp Ther 1997; 283: 1396–411.
McGehee DS . Molecular diversity of neuronal nicotinic acetylcholine receptors. Ann N Y Acad Sci 1999; 868: 565–77.
Freeman JA . Possible regulatory function of acetylcholine receptor in maintenance of retinotectal synapses. Nature 1977; 269: 218–22.
Chan J, Quik M . A role for the nicotinic α-bungarotoxin receptor in neurite outgrowth in PC12 cells. Neuroscience 1993; 56: 441–51.
Pugh PC, Berg DK . Neuronal acetylcholine receptors that bind α-bungarotoxin mediate neurite retraction in a calcium-dependent manner. J Neurosci 1994; 14: 889–96.
Renshaw GM . [125I]-α-bungarotoxin binding co-varies with motoneurone density during apoptosis. Neuroreport 1994; 5: 1949–52.
Hory-Lee F, Frank E . The nicotinic blocking agents d-tubocurare and α-bungarotoxin save motoneurons from naturally occurring death in the absence of neuromuscular blockade. J Neurosci 1995; 15: 6453–60.
Renshaw GM, Dyson SE . α-BTX lowers neuronal metabolism during the arrest of motoneurone apoptosis. Neuroreport 1995; 6: 284–8.
Treinin M, Chalfie M . A mutated acetylcholine receptor subunit causes neuronal degeneration in C elegans. Neuron 1995; 14: 871–7.
Wonnacott S, Drasdo A, Sanderson E, Rowell P . Presynapticnicotinic receptors and the modulation of transmitter release. Ciba Found Symp 1990; 152: 87–101; 102–5.
Alkondon M, Albuquerque EX . Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. J Pharmacol Exp Ther 1993; 265: 1455–73.
Alkondon M, Pereira EF, Albuquerque EX . Mapping the location of functional nicotinic and gamma-aminobutyric acid A receptors on hippocampal neurons. J Pharmacol Exp Ther 1996; 279: 1491–506.
Dani JA, Radcliffe KA, Pidoplichko VI . Variations in desensitization of nicotinic acetylcholine receptors from hippocampus andmidbrain dopamine areas. Eur J Pharmacol 2000; 393: 31–8.
Mike A, Castro NG, Albuquerque EX . Choline and acetylcholinehave similar kinetic properties of activation and desensitizationon the α7 nicotinic receptors in rat hippocampal neurons. Brain Res 2000; 882: 155–68.
Dani JA, De Biasi M . Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 2001; 70: 439–46.
Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Lena C, et al. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci 2003; 23: 7820–9.
Wu P, Ma D, Pierzchala M, Wu J, Yang LC, Mai X, et al. The Drosophila acetylcholine receptor subunit D β5 is part of an β-bungarotoxin binding acetylcholine receptor. J Biol Chem 2005; 280: 20987–94.
Wu M, Hajszan T, Leranth C, Alreja M . Nicotine recruits a local glutamatergic circuit to excite septohippocampal GAB Aergicneurons. Eur J Neurosci 2003; 18: 1155–68.
Thinschmidt JS, Frazier CJ, King MA, Meyer EM, Papke RL . Septal innervation regulates the function of α7 nicotinic receptors in CA1 hippocampal interneurons. Exp Neurol 2005; 195: 342–52.
Thinschmidt JS, Frazier CJ, King MA, Meyer EM, Papke RL . Medial septal/diagonal band cells express multiple functional nicotinic receptor subtypes that are correlated with firing frequency. Neurosci Lett 2005; 389: 163–8.
Fu W, Jhamandas JH . α-Amyloid peptide activates non-α7 nicotinic acetylcholine receptors in rat basal forebrain neurons. J Neurophysiol 2003; 90: 3130–6.
Granon S, Poucet B, Thinus-Blanc C, Changeux JP, Vidal C . Nicotinic and muscarinic receptors in the rat prefrontal cortex: differential roles in working memory, response selection and effortful processing. Psychopharmacology 1995; 119: 139–44.
Levin ED . Nicotinic systems and cognitive function. Psychopharmacology 1992; 108: 417–31.
Sugaya K, Giacobini E, Chiappinelli VA . Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease. J Neurosci Res 1990; 27: 349–59.
Rossner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V . The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signaling. Prog Neurobiol 1998; 56: 541–69.
Davies P, Maloney AJF . Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976; 2: 1403.
Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE . Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J Neurol Sci 1977; 34: 247–65.
Court J, Martin-Ruiz C, Piggott M, Spurden D, Griffiths M, Perry E . Nicotinic receptor abnormalities in Alzheimer's disease. Biol Psychiatry 2001; 49: 175–84.
Nordberg A . Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications. Biol Psychiatry 2001; 49: 200–10.
Nordberg A, Lundqvist H, Hartvig P, Andersson J, Johansson M, Hellstrom-Lindahi E, et al. Imaging of nicotinic and muscarinic receptors in Alzheimer's disease: effect of tacrine treatment. Dement Geriatr Cogn Disord 1997; 8: 78–84.
Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B . Kinetic analysis of regional (S)(-)11C-nicotine binding in normaland Alzheimer brains – in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 1995; 9: 21–7.
Martin-Ruiz CM, Court JA, Molnar E, Lee M, Gotti C, Mamalaki A, et al. A4 but not β3 and β7 nicotinic acetylcholine receptorsubunits are lost from the temporal cortex in Alzheimer's disease. J Neurochem 1999; 73: 1635–40.
Aubert L, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R . Comparative alterations of nicotinic and muscarinic bindingsites in Alzheimer's and Parkinson's diseases. J Neurochem 1992; 58: 529–41.
Hellstrom-Lindahl E, Mousavi M, Zhang X, Ravid R, Nordberg A . Regional distribution of nicotinic receptor subunit mRNAs in human brain: comparison between Alzheimer and normal brain. Brain Res Mol Brain Res 1999; 66: 94–103.
Mousavi M, Hellstrom-Lindahl E, Guan ZZ, Shan KR, Ravid R, Nordberg A . Protein and mRNA levels of nicotinic receptors inbrain of tobacco using controls and patients with Alzheimer's disease. Neuroscience 2003; 122: 515–20.
Terzano S, Court JA, Fornasari D, Griffiths M, Spurden DP, Lloyd S, et al. Expression of the ?.3 nicotinic receptor subunit mRNAin aging and Alzheimer's disease. Brain Res Mol Brain Res 1998; 63: 72–8.
Burghaus L, Schutz U, Krempel U, de Vos RA, Jansen Steur EN, Wevers A, et al. Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients. Brain Res Mol Brain Res 2000; 76: 385–8.
Sparks DL, Beach TG, Lukas RJ . Immunohistochemical localization of nicotinic ?.2 and β4 receptor subunits in normal humanbrain and individuals with Lewy body and Alzheimer's disease: preliminary observations. Neurosci Lett 1998; 256: 151–4.
Wevers A, Schroder H . Nicotinic acetylcholine receptors in Alzheimer's disease. J Alzheimers Dis 1999; 1: 207–19.
Zamani MR, Allen YS . Nicotine and its interaction with β-amyloid protein: a short review. Biol Psychiatry 2001; 49: 221–32.
Terry RD . The pathogenesis of Alzheimer disease: an alternativeto the amyloid hypothesis. J Neuropathol Exp Neurol 1996; 55: 1023–5.
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30: 572–80.
Klein WL . A β toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets. Neurochem Int 2002; 41: 345–52.
McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, et al. Soluble pool of Aβ amyloid as a determinant of severity of neuro degeneration in Alzheimer's disease. Ann Neurol 1999; 46: 860–6.
Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, et al. Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Path 1999; 155: 853–62.
Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 1999; 96: 3228–33.
Westerman MA, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin LH, et al. The relationship between A β and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 2002; 22: 1858–67.
D'Andrea MR, Cole GM, Ard MD . The microglial phagocyticrole with specific plaque types in the Alzheimer disease brain. Neurobiol Aging 2004; 25: 675–83.
McGeer PL, Klegeris A, Walker DG, Yasuhara O, McGeer EG . Pathological proteins in senile plaques. Tohoku J Exp Med 1994; 174: 269–77.
Anguiano M, Nowak RJ, Lansbury PT Jr . Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a pore-like mechanism that may be relevant to type II diabetes. Biochemistry 2002; 41: 11 338–43.
Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC . The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes 1999; 48: 491–8.
Mina EW, Demuro A, Kayed R, Milton S, Parker I, Glabe CG . Membrane disruption and elevated intracellular calcium as a common mechanism of amyloid oligomer-induced neurodegeneration. Neuroscience Abstracts 2004; 449: 20.
Bucciantini M, Calloni G, Chiti F, Formigli L, Nosi D, Dobson CM, et al. Prefibrillar amyloid protein aggregates share commonfeatures of cytotoxicity. J Biol Chem 2004; 279: 31 374–82.
Colom LV, Diaz ME, Beers DR, Neely A, Xie WJ, Appel SH, et al. Role of potassium channels in amyloid-induced cell death. J Neurochem 1998; 70: 1925–34.
Pike CJ, Balazs R, Cotman CW . Attenuation of β-amyloid neurotoxicity in vitro by potassium-induced depolarization. J Neurochem 1996; 67: 1774–7.
Dougherty JJ, Wu J, Nichols RA . β-Amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex. J Neurosci 2003; 30: 6740–7.
Grassi F, Palma E, Tonini R, Amici M, Ballivet M, Eusebi F . Amyloid α1–42 peptide alters the gating of human and mouse β-bungarotoxin-sensitive nicotinic receptors. J Physiol 2003; 547: 147–57.
Tozaki H, Matsumoto A, Kanno T, Nagai K, Nagata T, Yamamoto S, et al. The inhibitory and facilitatory actions of amyloid-β peptides on nicotinic ACh receptors and AMPA receptors. Biochem Biophys Res Commun 2002; 294: 42–5.
Wu J, Kuo YP, George AA, Xu L, Hu J, Lukas RJ . β-Amyloid directly inhibits human ?.4 β2–nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells. J Biol Chem 2004; 279: 37 842–51.
Magdesian MH, Nery AA, Martins AH, Juliano MA, Juliano L, Ulrich H, et al. Peptide blockers of the inhibition of neuronal nicotinic acetylcholine receptors by amyloid β. J Biol Chem 2005; 280: 31 085–90.
Avdulov NA, Chochina SV, Igbavboa U, O'Hare EO, Schroeder F, Cleary JP, et al. Amyloid β-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasmamembranes. J Neurochem 1997; 68: 2086–91.
Muller WE, Koch S, Eckert A, Hartmann H, Scheuer K . β-Amyloid peptide decreases membrane fluidity. Brain Res 1995; 674: 133–6.
Kanfer JN, Sorrentino G, Sitar DS . Amyloid beta peptide membrane perturbation is the basis for its biological effects. Neurochem Res 1999; 24: 1621–30.
Arispe N, Pollard HB, Rojas E . The ability of amyloid β-protein [A β P (1–40)] to form Ca2+channels provides a mechanism for neuronal death in Alzheimer's disease. Ann N Y Acad Sci 1994; 747: 256–66.
Sanderson KL, Butler L, Ingram VM . Aggregates of a β-amyloid peptide are required to induce calcium currents in neuron-likehuman teratocarcinoma cells: relation to Alzheimer's disease. Brain Res 1997; 744: 7–14.
Murray IV, Sindoni ME, Axelsen PH . Promotion of oxidativelipid membrane damage by amyloid β proteins. Biochemistry 2005; 44: 12606–13.
Tabner BJ, El-Agnaf OM, Turnbull S, German MJ, Paleologou KE, Hayashi Y, et al. Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J Biol Chem 2005; 280: 35 789–92.
Wang HY, Lee DH, D'Andrea MR, Peterson PA, Shank RP, Reitz AB . β-amyloid(1–42) binds to α7 nicotinic acetylcholinereceptor with high affinity: Implications for Alzheimer's disease pathology. J Biol Chem 2000; 275: 5626–32.
Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD . β-amyloid activates the mitogen-activated protein kinase cascade via hippocampal α7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer's disease. J Neurosci 2001; 21: 4125–33.
Mills J, Laurent Charest D, Lam F, Beyreuther K, Ida N, Pelech SL, et al. Regulation of amyloid precursor protein catabolism involves the mitogen-activated protein kinase signal transduction pathway. J Neurosci 1997; 17: 9415–22.
Nagele RG, D'Andrea MR, Anderson WJ, Wang HY . Intracellular accumulation of β-amyloid(1–42) in neurons is facilitated by the β 7 nicotinic acetylcholine receptor in Alzheimer's disease. Neuroscience 2002; 110: 199–211.
Michael R, D'Andrea, Daniel HSL, Wang HY, Nagele RG . Targeting intracellular Aβ42 for Alzheimer's disease. drug discovery. Drug Dev Res 2002; 56: 194–200.
Alkondon M, Braga MF, Pereira EF, Maelicke A, Albuquerque EX . α7 nicotinic acetylcholine receptors and modulation of GABAergic synaptic transmission in the hippocampus. Eur J Pharmacol 2000; 393: 59–67.
Kihara T, Shimohama S, Urushitani M, Sawada H, Kimura J, Kume T, et al. Stimulation of α4β2 nicotinic acetylcholine receptors inhibits β-amyloid toxicity. Brain Res 1998; 792: 331–4.
Burghaus L, Schutz U, Krempel U, de Vos RA, Jansen Steur EN, Wevers A, et al. Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimerpatients. Brain Res Mol Brain Res 2000; 76: 385–8.
Levin ED, Rezvani AH . Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord 2002; 1: 423–31.
Warpman U, Nordberg A . Epibatidine and ABT 418 reveal selective losses of α4β2 nicotinic receptors in Alzheimer brains. Neuroreport 1995; 6: 2419–23.
Rezvani AH, Levin ED . Cognitive effects of nicotine. Biol Psychiatry 2001; 49: 258–67.
Wang HY, Lee DH, Davis CB, Shank RP . Amyloid peptide Aβ(1–42) binds selectively and with picomolar affinity to α7 nicotinic acetylcholine receptors. J Neurochem 2000; 75: 1155–61.
Azam L, Winzer-Serhan U, Leslie FM . Co-expression of α7 andβ2 nicotinic acetylcholine receptor subunit mRNAs within ratbrain cholinergic neurons. Neuroscience 2003; 119: 965–77.
Khiroug SS, Harkness PC, Lamb PW, Sudweeks SN, Khiroug L, Millar NS, et al. Rat nicotinic ACh receptor ?.7 and β2 subunitsco-assemble to form functional heteromeric nicotinic receptorchannels. J Physiol 2002; 540: 425–34.
Dolezal V, Kasparova J . β-amyloid and cholinergic neurons. Neurochem Res 2003; 28: 499–506.
Selkoe DJ . Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 1999; 399: A23–31.
Fraser SP, Suh YH, Djamgoz MB . Ionic effects of the Alzheimer'sdisease β-amyloid precursor protein and its metabolic fragments. Trends Neurosci 1997; 20: 67–72.
Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM . Plasma and cerebrospinal fluid levels of amyloid β proteins 1–40 and 1–42 in Alzheimer disease. Arch Neurol 2000; 57: 100–5.
Kuo YM, Kokjohn TA, Kalback W, Luehrs D, Galasko DR, Chevallier N, et al. Amyloid-β peptides interact with plasmaproteins and erythrocytes: implications for their quantitationin plasma. Biochem Biophys Res Commun 2000; 268: 750–6.
Author information
Authors and Affiliations
Corresponding author
Additional information
Part of the work performed in Dr WU's laboratory was supported by an Arizona Alzheimer's Disease Core Center (ADCC) Pilot Research Grant.
Rights and permissions
About this article
Cite this article
Liu, Q., Wu, J. Neuronal nicotinic acetylcholine receptors serve as sensitive targets that mediate β-amyloid neurotoxicity. Acta Pharmacol Sin 27, 1277–1286 (2006). https://doi.org/10.1111/j.1745-7254.2006.00430.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00430.x
Keywords
This article is cited by
-
The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial
BMC Anesthesiology (2022)
-
ZY-1, A Novel Nicotinic Analog, Promotes Proliferation and Migration of Adult Hippocampal Neural Stem/Progenitor Cells
Cellular and Molecular Neurobiology (2013)
-
Nonlinear dynamical analysis of carbachol induced hippocampal oscillations in mice
Acta Pharmacologica Sinica (2009)
-
Acute β-Amyloid Administration Disrupts the Cholinergic Control of Dopamine Release in the Nucleus Accumbens
Neuropsychopharmacology (2008)