Abstract

α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein), are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

References

• 1. Adams C.E., Yonchek J.C., Schulz K.M., Graw S.L., Stitzel J., Teschke P.U., Stevens K.E.: Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases. Neuroscience, 2012; 207: 274-282
  Google Scholar
• 2. Addy N.A., Nakijama A., Levin E.D.: Nicotinic mechanisms of memory: effects of acute local DHβE and MLA infusions in the basolateral amygdala. Brain Res. Cogn. Brain Res., 2003; 16: 51-57
  Google Scholar
• 3. Akaike A., Takada-Takatori Y., Kume T., Izumi Y.: Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of α4 and α7 receptors in neuroprotection. J. Mol. Neurosci., 2010; 40: 211-216
  Google Scholar
• 4. Albuquerque E.X., Pereira E.F., Alkondon M., Rogers S.W.: Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol. Rev., 2009; 89: 73-120
  Google Scholar
• 5. Arias H.R., Gu R.X., Feuerbach D., Wei D.Q.: Different interaction between the agonist JN403 and the competitive antagonist methyllycaconitine with the human α7 nicotinic acetylcholine receptor. Biochemistry, 2010; 49: 4169-4180
  Google Scholar
• 6. Arneric S.P., Sullivan J.P., Briggs C.A., Donnelly-Roberts D., Anderson D.J., Raszkiewicz J.L., Hughes M.L., Cadman E.D., Adams P., Garvey D.S.: (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization. J. Pharmacol. Exp. Ther., 1994; 270: 310-318
  Google Scholar
• 7. Bettany J.H., Levin E.D.: Ventral hippocampal α7 nicotinic receptor blockade and chronic nicotine effects on memory performance in the radial-arm maze. Pharmacol. Biochem. Behav., 2001; 70: 467-474
  Google Scholar
• 8. Bitner R.S., Bunnelle W.H., Anderson D.J., Briggs C.A., Buccafusco J., Curzon P., Decker M.W., Frost J.M., Gronlien J.H., Gubbins E., Li J., Malysz J., Markosyan S., Marsh K., Meyer M.D. i wsp.: Broad- -spectrum efficacy across cognitive domains by α7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J. Neurosci., 2007; 27: 10578-10587
  Google Scholar
• 9. Bitner R.S., Nikkel A.L., Markosyan S., Otte S., Puttfarcken P., Gopalakrishnan M.: Selective α7 nicotinic acetylcholine receptor activation regulates glycogen synthase kinase3β and decreases tau phosphorylation in vivo. Brain Res., 2009; 1265: 65-74
  Google Scholar
• 10. Boccia M.M., Blake M.G., Krawczyk M.C., Baratti C.M.: Hippocampal α7 nicotinic receptors modulate memory reconsolidation of an inhibitory avoidance task in mice. Neuroscience, 2010; 171: 531-543
  Google Scholar
• 11. Bordia T., Grady S.R., McIntosh J.M., Quik M.: Nigrostriatal damage preferentially decreases a subpopulation of α6β2* nAChRs in mouse, monkey, and Parkinson’s disease striatum. Mol. Pharmacol., 2007; 72: 52-61
  Google Scholar
• 12. Callahan P.M., Hutchings E.J., Kille N.J., Chapman J.M., Terry A.V. Jr.: Positive allosteric modulator of α7 nicotinic-acetylcholine receptors, PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates. Neuropharmacology, 2013; 67: 201-212
  Google Scholar
• 13. Castner S.A., Smagin G.N., Piser T.M., Wang Y., Smith J.S., Christian E.P., Mrzljak L., Williams G.V.: Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors. Biol. Psychiatry, 2011; 69: 12-18
  Google Scholar
• 14. Chan W.K., Wong P.T., Sheu F.S.: Frontal cortical α7 and α4β2 nicotinic acetylcholine receptors in working and reference memory. Neuropharmacology, 2007; 52: 1641-1649
  Google Scholar
• 15. Changeux J.P.: The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J. Biol. Chem., 2012; 287: 40207-40215
  Google Scholar
• 16. Court J., Spurden D., Lloyd S., McKeith I., Ballard C., Cairns N., Kerwin R., Perry R., Perry E.: Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: α-bungarotoxin and nicotine binding in the thalamus. J. Neurochem., 1999; 73: 1590-1597
  Google Scholar
• 17. Curzon P., Anderson D.J., Nikkel A.L., Fox G.B., Gopalakrishnan M., Decker M.W., Bitner R.S.: Antisense knockdown of the rat α7 nicotinic acetylcholine receptor produces spatial memory impairment. Neurosci. Lett., 2006; 410: 15-19
  Google Scholar
• 18. Dani J.A.: Overview of nicotinic receptors and their roles in the central nervous system. Biol. Psychiatry, 2001; 49: 166-174
  Google Scholar
• 19. Deardorff W.J., Shobassy A., Grossberg G.T.: Safety and clinical effects of EVP-6124 in subjects with Alzheimer’s disease currently or previously receiving an acetylcholinesterase inhibitor medication. Expert Rev. Neurother., 2015; 15: 7-17
  Google Scholar
• 20. Decker M.W., Brioni J.D., Sullivan J.P., Buckley M.J., Radek R.J., Raszkiewicz J.L., Kang C.H., Kim D.J., Giardina W.J., Wasicak J.T.: (S)- -3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J. Pharmacol. Exp. Ther., 1994; 270: 319-328
  Google Scholar
• 21. Dépatie L., O’Driscoll G.A., Holahan A.L., Atkinson V., Thavundayil J.X., Kin N.N., Lal S.: Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study. Neuropsychopharmacology, 2002; 27: 1056-1070
  Google Scholar
• 22. Deutsch S.I., Burket J.A., Benson A.D., Urbano M.R.: The 15q13.3 deletion syndrome: Deficient α7 -containing nicotinic acetylcholine receptor-mediated neurotransmission in the pathogenesis of neurodevelopmental disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016; 64: 109-117
  Google Scholar
• 23. Dinklo T., Shaban H., Thuring J.W., Lavreysen H., Stevens K.E., Zheng L., Mackie C., Grantham C., Vandenberk I., Meulders G., Peeters L., Verachtert H., De Prins E., Lesage A.S.: Characterization of 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)- -5-thiazolemethanol (JNJ-1930942), a novel positive allosteric modulator of the α7 nicotinic acetylcholine receptor. J. Pharmacol. Exp. Ther., 2011; 336: 560-574
  Google Scholar
• 24. Dziewczapolski G., Glogowski C.M., Masliah E., Heinemann S.F.: Deletion of the α7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer’s disease. J. Neurosci., 2009; 29: 8805-8815
  Google Scholar
• 25. Faludi G., Dome P., Lazary J.: Origins and perspectives of schizophrenia research. Neuropsychopharmacol. Hung., 2011; 13: 185-192
  Google Scholar
• 26. Fehér A., Juhász A., Rimanóczy A., Csibri E., Kálmán J., Janka Z.: Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia. Dement. Geriatr. Cogn. Disord., 2009; 28: 56-62
  Google Scholar
• 27. Fernandes C., Hoyle E., Dempster E., Schalkwyk L.C., Collier D.A.: Performance deficit of α7 nicotinic receptor knockout mice in a delayed matching-to-place task suggests a mild impairment of working/episodic-like memory. Genes Brain Behav., 2006; 5: 433-440
  Google Scholar
• 28. Feuerbach D., Lingenhoehl K., Olpe H.R., Vassout A., Gentsch C., Chaperon F., Nozulak J., Enz A., Bilbe G., McAllister K., Hoyer D.: The selective nicotinic acetylcholine receptor α7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain. Neuropharmacology, 2009; 56: 254-263
  Google Scholar
• 29. Fodero L.R., Mok S.S., Losic D., Martin L.L., Aguilar M.I., Barrow C.J., Livett B.G., Small D.H.: α7-nicotinic acetylcholine receptors mediate an Aβ1-42-induced increase in the level of acetylcholinesterase in primary cortical neurones. J. Neurochem., 2004; 88: 1186-1193
  Google Scholar
• 30. Freedman R., Hall M., Adler L.E., Leonard S.: Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol. Psychiatry, 1995; 38: 22-33
  Google Scholar
• 31. Freedman R., Olincy A., Buchanan R.W., Harris J.G., Gold J.M., Johnson L., Allensworth D., Guzman-Bonilla A., Clement B., Ball M.P., Kutnick J., Pender V., Martin L.F., Stevens K.E., Wagner B.D., Zerbe G.O., Soti F., Kem W.R.: Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am. J. Psychiatry, 2008; 165: 1040-1047
  Google Scholar
• 32. Gehricke J.G., Hong N., Whalen C.K., Steinhoff K., Wigal T.L.: Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychol. Addict. Behav., 2009; 23: 644-655
  Google Scholar
• 33. Gill J.K., Chatzidaki A., Ursu D., Sher E., Millar N.S.: Contrasting properties of α7-selective orthosteric and allosteric agonists examined on native nicotinic acetylcholine receptors. PLoS One, 2013; 8: e55047
  Google Scholar
• 34. Gómez-Isla T., Hollister R., West H., Mui S., Growdon J.H., Petersen R.C., Parisi J.E., Hyman B.T.: Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann. Neurol., 1997; 41: 17-24
  Google Scholar
• 35. Gotti C., Clementi F.: Neuronal nicotinic receptors: from structure to pathology. Prog. Neurobiol., 2004; 74: 363-396
  Google Scholar
• 36. Grady S.R., Salminen O., Laverty D.C., Whiteaker P., McIntosh J.M., Collins A.C., Marks M.J.: The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum. Biochem. Pharmacol., 2007; 74: 1235-1246
  Google Scholar
• 37. Guan Z.Z., Zhang X., Blennow K., Nordberg A.: Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. Neuroreport, 1999; 10: 1779-1782
  Google Scholar
• 38. Guan Z.Z., Zhang X., Ravid R., Nordberg A.: Decreased protein levels of nicotinic receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer’s disease. J. Neurochem., 2000; 74: 237-243
  Google Scholar
• 39. Hardy J.: A hundred years of Alzheimer’s disease research. Neuron, 2006; 52: 3-13
  Google Scholar
• 40. Hashimoto K., Fujita Y., Ishima T., Hagiwara H., Iyo M.: Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of tropisetron: role of α7 nicotinic receptors. Eur. J. Pharmacol., 2006; 553: 191-195
  Google Scholar
• 41. Hauser T.A., Kucinski A., Jordan K.G., Gatto G.J., Wersinger S.R., Hesse R.A., Stachowiak E.K., Stachowiak M.K., Papke R.L., Lippiello P.M., Bencherif M.: TC-5619: an alpha7 neuronal nicotinic receptor- -selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia. Biochem. Pharmacol., 2009; 78: 803-812
  Google Scholar
• 42. Hellström-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
  Google Scholar
• 43. Hoyle E., Genn R.F., Fernandes C., Stolerman I.P.: Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Psychopharmacology, 2006; 189: 211-223
  Google Scholar
• 44. Huang M., Felix A.R., Kwon S., Lowe D., Wallace T., Santarelli L., Meltzer H.Y.: The alpha-7 nicotinic receptor partial agonist/5-HT3 antagonist RG3487 enhances cortical and hippocampal dopamine and acetylcholine release. Psychopharmacology, 2014; 231: 2199-2210
  Google Scholar
• 45. Huang X., Cheng Z., Su Q., Zhu X., Wang Q., Chen R., Wang X.: Neuroprotection by nicotine against colchicine-induced apoptosis is mediated by PI3-kinase – Akt pathways. Int. J. Neurosci., 2012; 122: 324-332
  Google Scholar
• 46. Janhunen S., Ahtee L.: Differential nicotinic regulation of the nigrostriatal and mesolimbic dopaminergic pathways: implications for drug development. Neurosci. Biobehav. Rev., 2007; 31: 287-314
  Google Scholar
• 47. Jubelt L.E., Barr R.S., Goff D.C., Logvinenko T., Weiss A.P., Evins A.E.: Effects of transdermal nicotine on episodic memory in nonsmokers with and without schizophrenia. Psychopharmacology, 2008; 199: 89-98
  Google Scholar
• 48. Kalappa B.I., Uteshev V.V.: The dual effect of PNU-120596 on α7 nicotinic acetylcholine receptor channels. Eur. J. Pharmacol., 2013; 718: 226-234
  Google Scholar
• 49. Kawamata J., Suzuki S., Shimohama S.: α7 nicotinic acetylcholine receptor mediated neuroprotection in Parkinson’s disease. Curr. Drug Targets, 2012; 13: 623-630
  Google Scholar
• 50. Kihara T., Shimohama S., Sawada H., Honda K., Nakamizo T., Shibasaki H., Kume T., Akaike A.: α7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block Aβ-amyloid-induced neurotoxicity. J. Biol. Chem., 2001; 276: 13541-13546
  Google Scholar
• 51. Kitagawa H., Takenouchi T., Azuma R., Wesnes K.A., Kramer W.G., Clody D.E., Burnett A.L.: Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. Neuropsychopharmacology, 2003; 28: 542-551
  Google Scholar
• 52. Kohnomi S., Suemaru K., Goda M., Choshi T., Hibino S., Kawasaki H., Araki H.: Ameliorating effects of tropisetron on dopaminergic disruption of prepulse inhibition via the α7 nicotinic acetylcholine receptor in Wistar rats. Brain Res., 2010; 1353: 152-158
  Google Scholar
• 53. Konradsson-Geuken A., Gash C.R., Alexander K., Pomerleau F., Huettl P., Gerhardt G.A., Bruno J.P.: Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats. Synapse, 2009; 63: 1069-1082
  Google Scholar
• 54. Lee D.H., Wang H.Y.: Differential physiologic responses of α7 nicotinic acetylcholine receptors to β-amyloid1-40 and β-amyloid1-42. J. Neurobiol., 2003; 55: 25-30
  Google Scholar
• 55. Leiser S.C., Bowlby M.R., Comery T.A., Dunlop J.: A cog in cognition: how the α7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits. Pharmacol. Ther., 2009; 122: 302-311
  Google Scholar
• 56. Levin E.D., Bettegowda C., Blosser J., Gordon J.: AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats. Behav. Pharmacol., 1999; 10: 675-680
  Google Scholar
• 57. Levin E.D., Bradley A., Addy N., Sigurani N.: Hippocampal α7 and α4β2 nicotinic receptors and working memory. Neuroscience, 2002; 109: 757-65
  Google Scholar
• 58. Levin E.D., Conners C.K., Silva D., Hinton S.C., Meck W.H., March J., Rose J.E.: Transdermal nicotine effects on attention. Psychopharmacology, 1998; 140: 135-141
  Google Scholar
• 59. Levin E.D., Conners C.K., Sparrow E., Hinton S.C., Erhardt D., Meck W.H., Rose J.E., March J.: Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology, 1996; 123: 55-63
  Google Scholar
• 60. Levin E.D., Petro A., Rezvani A.H., Pollard N., Christopher N.C., Strauss M., Avery J., Nicholson J., Rose J.E.: Nicotinic α7- or β2- containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice. Behav. Brain Res., 2009; 196: 207-213
  Google Scholar
• 61. Levin E.D., Wilson W., Rose J.E., McEvoy J.: Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacology, 1996; 15: 429-436
  Google Scholar
• 62. Li X., Rainnie D.G., McCarley R.W., Greene R.W.: Presynaptic nicotinic receptors facilitate monoaminergic transmission. J. Neurosci., 1998; 18: 1904-1912
  Google Scholar
• 63. Lieberman J.A., Dunbar G., Segreti A.C., Girgis R.R., Seoane F., Beaver J.S., Duan N., Hosford D.A.: A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology, 2013; 38: 968-975
  Google Scholar
• 64. Lilja A.M., Porras O., Storelli E., Nordberg A., Marutle A.: Functional interactions of fibrillar and oligomeric amyloid-β with α7 nicotinic receptors in Alzheimer’s disease. J. Alzheimers Dis., 2011; 23: 335-347
  Google Scholar
• 65. Liu Q., Kawai H., Berg D.K.: β-Amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons. Proc. Natl. Acad. Sci. USA, 2001; 98: 4734-4739
  Google Scholar
• 66. Livingstone P.D., Srinivasan J., Kew J.N., Dawson L.A., Gotti C., Moretti M., Shoaib M., Wonnacott S.: α7 and non-α7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex. Eur. J. Neurosci., 2009; 29: 539-550
  Google Scholar
• 67. Lopes C., Pereira E.F., Wu H.Q., Purushottamachar P., Njar V., Schwarcz R., Albuquerque E.X.: Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at α7* nicotinic receptors. J. Pharmacol. Exp. Ther., 2007; 322: 48-58
  Google Scholar
• 68. Machaalani R., Kashi P.K., Waters K.A.: Distribution of nicotinic acetylcholine receptor subunits α7 and β2 in the human brainstem and hippocampal formation. J. Chem. Neuroanat., 2010; 40: 223-231
  Google Scholar
• 69. Malysz J., Gronlien J.H., Timmermann D.B., Hakerud M., Thorin-Hagene K., Ween H., Trumbull J.D., Xiong Y., Briggs C.A., Ahring P.K., Dyhring T., Gopalakrishnan M.: Evaluation of α7 nicotinic acetylcholine receptor agonists and positive allosteric modulators using the parallel oocyte electrophysiology test station. Assay Drug Dev. Technol., 2009; 7: 374-390
  Google Scholar
• 70. Marighetto A., Valerio S., Desmedt A., Philippin J.N., Trocmé-Thibierge C., Morain P.: Comparative effects of the α7 nicotinic partial agonist, S 24795, and the cholinesterase inhibitor, donepezil, against aging-related deficits in declarative and working memory in mice. Psychopharmacology, 2008; 197: 499-508
  Google Scholar
• 71. Martin-Ruiz C.M., Haroutunian V.H., Long P., Young A.H., Davis K.L., Perry E.K., Court J.A.: Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol. Psychiatry, 2003; 54: 1222-1233
  Google Scholar
• 72. Marutle A., Zhang X., Court J., Piggott M., Johnson M., Perry R., Perry E., Nordberg A.: Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J. Chem. Neuroanat., 2001; 22: 115-126
  Google Scholar
• 73. Mazurov A.A., Kombo D.C., Hauser T.A., Miao L., Dull G., Genus J.F., Fedorov N.B., Benson L., Sidach S., Xiao Y., Hammond P.S., James J.W., Miller C.H., Yohannes D.: Discovery of (2S,3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders. J. Med. Chem., 2012; 55: 9793-9809
  Google Scholar
• 74. Morens D.M., Grandinetti A., Reed D., White L.R., Ross G.W.: Cigarette smoking and protection from Parkinson’s disease: false association or etiologic clue? Neurology, 1995; 45: 1041-1051
  Google Scholar
• 75. Nagele R.G., D’Andrea M.R., Anderson W.J., Wang H.Y.: Intracellular accumulation of β-amyloid1-42 in neurons is facilitated by the α7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience, 2002; 110: 199-211
  Google Scholar
• 76. Nordberg A.: Nicotinic receptor abnormalities of Alzheimer’s disease: therapeutic implications. Biol. Psychiatry, 2001; 49: 200-210
  Google Scholar
• 77. Nott A., Levin E.D.: Dorsal hippocampal α7 and α4β2 nicotinic receptors and memory. Brain Res., 2006; 1081: 72-78
  Google Scholar
• 78. Olincy A., Harris J.G., Johnson L.L., Pender V., Kongs S., Allensworth D., Ellis J., Zerbe G.O., Leonard S., Stevens K.E., Stevens J.O., Martin L., Adler L.E., Soti F., Kem W.R., Freedman R.: Proof-of-concept trial of an α7 nicotinic agonist in schizophrenia. Arch. Gen. Psychiatry, 2006; 63: 630-638
  Google Scholar
• 79. Othman A.A., Lenz R.A., Zhang J., Li J., Awni W.M., Dutta S.: Single- and multiple-dose pharmacokinetics, safety, and tolerability of the selective α7 neuronal nicotinic receptor agonist, ABT-107, in healthy human volunteers. J. Clin. Pharmacol., 2011; 51: 512-526
  Google Scholar
• 80. Papke R.L.: Merging old and new perspectives on nicotinic acetylcholine receptors. Biochem. Pharmacol., 2014; 89: 1-11
  Google Scholar
• 81. Papke R.L., Thinschmidt J.S., Moulton B.A., Meyer E.M., Poirier A.: Activation and inhibition of rat neuronal nicotinic receptors by ABT-418. Br. J. Pharmacol., 1997; 120: 429-438
  Google Scholar
• 82. Parikh V., Kutlu M.G., Gould T.J.: nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives. Schizophr. Res., 2016; 171: 1-15
  Google Scholar
• 83. Perry E.K., Morris C.M., Court J.A., Cheng A., Fairbairn A.F., McKeith I.G., Irving D., Brown A., Perry R.H.: Alteration in nicotine binding sites in Parkinson’s disease, Lewy body dementia and Alzheimer’s disease: possible index of early neuropathology. Neuroscience, 1995; 64: 385-395
  Google Scholar
• 84. Pettit D.L., Shao Z., Yakel J.L.: β-Amyloid1-42 peptide directly modulates nicotinic receptors in the rat hippocampal slice. J. Neurosci., 2001; 21: RC120
  Google Scholar
• 85. Pichat P., Bergis O.E., Terranova J.P., Urani A., Duarte C., Santucci V., Gueudet C., Voltz C., Steinberg R., Stemmelin J., Oury-Donat F., Avenet P., Griebel G., Scatton B.: SSR180711, a novel selective α7 nicotinic receptor partial agonist: (II) efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia. Neuropsychopharmacology, 2007; 32: 17-34
  Google Scholar
• 86. Posadas I., López-Hernández B., Cena V.: Nicotinic receptors in neurodegeneration. Curr. Neuropharmacol., 2013; 11: 298-314
  Google Scholar
• 87. Potter A., Corwin J., Lang J., Piasecki M., Lenox R., Newhouse P.A.: Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer’s disease. Psychopharmacology, 1999; 142: 334-342
  Google Scholar
• 88. Preskorn S.H., Gawryl M., Dgetluck N., Palfreyman M., Bauer L.O., Hilt D.C.: Normalizing effects of EVP-6124, an α-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J. Psychiatr. Pract., 2014; 20: 12-24
  Google Scholar
• 89. Prickaerts J., van Goethem N.P., Chesworth R., Shapiro G., Boess F.G., Methfessel C., Reneerkens O.A., Flood D.G., Hilt D., Gawryl M., Bertrand S., Bertrand D., König G.: EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors. Neuropharmacology, 2012; 62: 1099-1110
  Google Scholar
• 90. Quik M., Huang L.Z., Parameswaran N., Bordia T., Campos C., Perez X.A.: Multiple roles for nicotine in Parkinson’s disease. Biochem. Pharmacol., 2009; 78: 677-685
  Google Scholar
• 91. Ray M.A., Graham A.J., Lee M., Perry R.H., Court J.A., Perry E.K.: Neuronal nicotinic acetylcholine receptor subunits in autism: an immunohistochemical investigation in the thalamus. Neurobiol. Dis., 2005; 19: 366-377
  Google Scholar
• 92. Redrobe J.P., Nielsen E.O., Christensen J.K., Peters D., Timmermann D.B., Olsen G.M.: α7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a modified continuous Y-maze task in mice. Eur. J. Pharmacol., 2009; 602: 58-65
  Google Scholar
• 93. Ren K., Thinschmidt J., Liu J., Ai L., Papke R.L., King M.A., Hughes J.A., Meyer E.M.: α7 Nicotinic receptor gene delivery into mouse hippocampal neurons leads to functional receptor expression, improved spatial memory-related performance, and tau hyperphosphorylation. Neuroscience, 2007; 145: 314-322
  Google Scholar
• 94. Rezvani A.H., Eddins D., Slade S., Hampton D.S., Christopher N.C., Petro A., Horton K., Johnson M., Levin E.D.: Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: persisting effects on locomotor activity, learning and nicotine self-administration. Neuroscience, 2008; 154: 885-897
  Google Scholar
• 95. Rezvani A.H., Kholdebarin E., Brucato F.H., Callahan P.M., Lowe D.A., Levin E.D.: Effect of R3487/MEM3454, a novel nicotinic α7 receptor partial agonist and 5-HT3 antagonist on sustained attention in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009; 33: 269-275
  Google Scholar
• 96. Roncarati R., Scali C., Comery T.A., Grauer S.M., Aschmi S., Bothmann H., Jow B., Kowal D., Gianfriddo M., Kelley C., Zanelli U., Ghiron C., Haydar S., Dunlop J., Terstappen G.C.: Procognitive and neuroprotective activity of a novel α7 nicotinic acetylcholine receptor agonist for treatment of neurodegenerative and cognitive disorders. J. Pharmacol. Exp. Ther., 2009; 329: 459-468
  Google Scholar
• 97. Sberna G., Sáez-Valero J., Beyreuther K., Masters C.L., Small D.H.: The amyloid β-protein of Alzheimer’s disease increases acetylcholinesterase expression by increasing intracellular calcium in embryonal carcinoma P19 cells. J. Neurochem., 1997; 69: 1177-1184
  Google Scholar
• 98. Schicker K.W., Dorostkar M.M., Boehm S.: Modulation of transmitter release via presynaptic ligand-gated ion channels. Curr. Mol. Pharmacol., 2008; 1: 106-129
  Google Scholar
• 99. Shen H., Kihara T., Hongo H., Wu X., Kem W.R., Shimohama S., Akaike A., Niidome T., Sugimoto H.: Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of α7 nicotinic receptors and internalization of NMDA receptors. Br. J. Pharmacol., 2010; 161: 127-139
  Google Scholar
• 100. Shinotoh H., Namba H., Fukushi K., Nagatsuka S., Tanaka N., Aotsuka A., Ota T., Tanada S., Irie T.: Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer’s disease: a positron emission tomography study. Ann. Neurol., 2000; 48: 194-200
  Google Scholar
• 101. Shytle R.D., Mori T., Townsend K., Vendrame M., Sun N., Zeng J., Ehrhart J., Silver A.A., Sanberg P.R., Tan J.: Cholinergic modulation of microglial activation by α7 nicotinic receptors. J. Neurochem., 2004; 89: 337-343
  Google Scholar
• 102. Sinkus M.L., Graw S., Freedman R., Ross R.G., Lester H.A., Leonard S.: The human CHRNA7 and CHRFAM7A genes: a review of the genetics, regulation, and function. Neuropharmacology, 2015; 96: 274-288
  Google Scholar
• 103. Small D.H., Maksel D., Kerr M.L., Ng J., Hou X., Chu C., Mehrani H., Unabia S., Azari M.F., Loiacono R., Aguilar M.I., Chebib M.: The β-amyloid protein of Alzheimer’s disease binds to membrane lipids but does not bind to the α7 nicotinic acetylcholine receptor. J. Neurochem., 2007; 101: 1527-1538
  Google Scholar
• 104. Sydserff S., Sutton E.J., Song D., Quirk M.C., Maciag C., Li C., Jonak G., Gurley D., Gordon J.C., Christian E.P., Doherty J.J., Hudzik T., Johnson E., Mrzljak L., Piser T. i wsp.: Selective α7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes. Biochem. Pharmacol., 2009; 78: 880-888
  Google Scholar
• 105. Takada-Takatori Y., Kume T., Sugimoto M., Katsuki H., Niidome T., Sugimoto H., Fujii T., Okabe S., Akaike A.: Neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity. Eur. J. Pharmacol., 2006; 549: 19-26
  Google Scholar
• 106. Terry A.V. Jr, Decker M.W.: Neurobiology of nAChRs and cognition: a mini review of Dr. Jerry J. Buccafusco’s contributions over a 25 year career. Biochem. Pharmacol., 2011; 82: 883-890
  Google Scholar
• 107. Tietje K.R., Anderson D.J., Bitner R.S., Blomme E.A., Brackemeyer P.J., Briggs C.A., Browman K.E., Bury D., Curzon P., Drescher K.U., Frost J.M., Fryer R.M., Fox G.B., Gronlien J.H., Hakerud M. i wsp.: Preclinical characterization of A-582941: a novel α7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties. CNS Neurosci. Ther., 2008; 14: 65-82
  Google Scholar
• 108. Timmermann D.B., Gronlien J.H., Kohlhaas K.L., Nielsen E.O., Dam E., Jorgensen T.D., Ahring P.K., Peters D., Holst D., Christensen J.K., Malysz J., Briggs C.A., Gopalakrishnan M., Olsen G.M.: An allosteric modulator of the α7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J. Pharmacol. Exp. Ther., 2007; 323: 294-307
  Google Scholar
• 109. Toyohara J., Wu J., Hashimoto K.: Recent development of radioligands for imaging α7 nicotinic acetylcholine receptors in the brain. Curr. Top Med. Chem., 2010; 10: 1544-1557
  Google Scholar
• 110. Van Kampen M., Selbach K., Schneider R., Schiegel E., Boess F., Schreiber R.: AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors. Psychopharmacology, 2004; 172: 375-383
  Google Scholar
• 111. Vicens P., Ribes D., Torrente M., Domingo J.L.: Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice. Behav Brain Res, 2011; 216: 341-348
  Google Scholar
• 112. Vijayaraghavan S., Pugh P.C., Zhang Z.W., Rathouz M.M., Berg D.K.: Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free Ca2+. Neuron, 1992; 8: 353-362
  Google Scholar
• 113. Wallace T.L., Callahan P.M., Tehim A., Bertrand D., Tombaugh G., Wang S., Xie W., Rowe W.B., Ong V., Graham E., Terry A.V. Jr, Rodefer J.S., Herbert B., Murray M., Porter R., Santarelli L., Lowe D.A.: RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents. J. Pharmacol. Exp. Ther., 2011; 336: 242-253
  Google Scholar
• 114. Walling D., Marder S.R., Kane J., Fleischhacker W.W., Keefe R.S., Hosford D.A., Dvergsten C., Segreti A.C., Beaver J.S., Toler S.M., Jett J.E., Dunbar G.C.: Phase 2 trial of an alpha-7 nicotinic receptor agonist (TC-5619) in negative and cognitive symptoms of schizophrenia. Schizophr. Bull., 2016; 42: 335-343
  Google Scholar
• 115. Wang H., Yu M., Ochani M., Amella C.A., Tanovic M., Susarla S., Li J.H., Wang H., Yang H., Ulloa L., Al-Abed Y., Czura C.J., Tracey K.J.: Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature, 2003; 421: 384-388
  Google Scholar
• 116. Wang H.Y., Lee D.H., D’Andrea M.R., Peterson P.A., Shank R.P., Reitz A.B.: β-Amyloid1-42 binds to αa7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer’s disease pathology. J. Biol. Chem., 2000; 275: 5626-5632
  Google Scholar
• 117. Wang H.Y., Lee D.H., Davis C.B., Shank R.P.: Amyloid peptide Aβ1-42 binds selectively and with picomolar affinity to α7 nicotinic acetylcholine receptors. J. Neurochem., 2000; 75: 1155-1161
  Google Scholar
• 118. Wang H.Y., Stucky A., Liu J., Shen C., Trocme-Thibierge C., Morain P.: Dissociating β-amyloid from α7 nicotinic acetylcholine receptor by a novel therapeutic agent, S 24795, normalizes α7 nicotinic acetylcholine and NMDA receptor function in Alzheimer’s disease brain. J. Neurosci., 2009; 29: 10961-10973
  Google Scholar
• 119. Werkheiser J.L., Sydserff S., Hubbs S.J., Ding M., Eisman M.S., Perry D., Williams A.J., Smith J.S., Mrzljak L., Maier D.L.: Ultra-low exposure to alpha-7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in alpha-7 receptor expression in rodents: implications for low dose clinical efficacy. Neuroscience, 2011; 186: 76-87
  Google Scholar
• 120. Wevers A., Monteggia L., Nowacki S., Bloch W., Schütz U., Lindstrom J., Pereira E.F., Eisenberg H., Giacobini E., de Vos R.A., Steur E.N., Maelicke A., Albuquerque E.X., Schröder H.: Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer’s disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein. Eur. J. Neurosci., 1999; 11: 2551-2565
  Google Scholar
• 121. White H.K., Levin E.D.: Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology, 1999; 143: 158-165
  Google Scholar
• 122. White H.K., Levin E.D.: Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment. Psychopharmacology, 2004; 171: 465-471
  Google Scholar
• 123. Wilens T.E., Biederman J., Spencer T.J., Bostic J., Prince J., Monuteaux M.C., Soriano J., Fine C., Abrams A., Rater M., Polisner D.: A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am. J. Psychiatry, 1999; 156: 1931-1937
  Google Scholar
• 124. Wu J., Liu Q., Tang P., Mikkelsen J.D., Shen J., Whiteaker P., Yakel J.L.: Heteromeric α7β2 nicotinic acetylcholine receptors in the brain. Trends Pharmacol. Sci., 2016; 37: 562-574
  Google Scholar
• 125. Wu J., Lukas R.J.: Naturally-expressed nicotinic acetylcholine receptor subtypes. Biochem. Pharmacol., 2011; 82: 800-807
  Google Scholar
• 126. Yasui D.H., Scoles H.A., Horike S., Meguro-Horike M., Dunaway K.W., Schroeder D.I., Lasalle J.M.: 15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Hum. Mol. Genet., 2011; 20: 4311-4323
  Google Scholar
• 127. Young J.W., Crawford N., Kelly J.S., Kerr L.E., Marston H.M., Spratt C., Finlayson K., Sharkey J.: Impaired attention is central to the cognitive deficits observed in alpha 7 deficient mice. Eur. Neuropsychopharmacol., 2007; 17: 145-155
  Google Scholar
• 128. Young J.W., Geyer M.A.: Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem. Pharmacol., 2013; 86: 1122-1132
  Google Scholar
• 129. Zammit S., Allebeck P., Dalman C., Lundberg I., Hemmingsson T., Lewis G.: Investigating the association between cigarette smoking and schizophrenia in a cohort study. Am. J. Psychiatry, 2003; 160: 2216-2221
  Google Scholar

Full text