Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Perspective

Nicotine Abuse and Neurodegeneration: Novel Pharmacogenetic Targets to Aid Quitting and Reduce the Risk of Dementia

Author(s): Fatimah Almahasneh, Romany H. Gerges, Ejlal Abu-El-Rub* and Ramada R. Khasawneh

Volume 23, Issue 1, 2024

Published on: 08 March, 2023

Page: [2 - 8] Pages: 7

DOI: 10.2174/1871527322666230220121655

conference banner
Abstract

Nicotine dependence has deleterious neurological impacts. Previous studies found an association between cigarette smoking and accelerating age-related thinning of the brain's cortex and subsequent cognitive decline. Smoking is considered the third most common risk factor for dementia, which prompted the inclusion of smoking cessation in dementia prevention strategies. Traditional pharmacologic options for smoking cessation include nicotine transdermal patches, bupropion and varenicline. However, based on smokers’ genetic makeup, pharmacogenetics can be used to develop novel therapies to replace these traditional approaches. Genetic variability of cytochrome P450 2A6 has a major impact on smokers’ behavior and their response to quitting therapies. Gene polymorphism in nicotinic acetylcholine receptor subunits also has a great influence on the ability to quit smoking. In addition, polymorphism of certain nicotinic acetylcholine receptors was found to affect the risk of dementia and the impact of tobacco smoking on the development of Alzheimer's disease. Nicotine dependence involves the activation of pleasure response through the stimulation of dopamine release. Central dopamine receptors, catechol-o-methyltransferase and the dopamine transporter protein, regulate synaptic dopamine levels. The genes of these molecules are potential targets for novel smoking cessation drugs. Pharmacogenetic studies of smoking cessation also investigated other molecules, such as ANKK1 and dopamine-beta-hydroxylase (DBH). In this perspective article, we aim to highlight the promising role of pharmacogenetics in the development of effective drugs for smoking cessation, which can increase the success rate of smoking quitting plans and ultimately reduce the incidence of neurodegeneration and dementia.

Keywords: Nicotine abuse, neurodegeneration, dementia, pharmacogenetics, dopamine, prevention.

« Previous Next »
Graphical Abstract

[1]
García-Gómez L, Hernández-Pérez A, Noé-Díaz V, Riesco-Miranda JA, Jiménez-Ruiz C. Smoking cessation treatments: Current psychological and pharmacological options. Rev Invest Clin 2019; 71(1): 7-16.
[http://dx.doi.org/10.24875/RIC.18002629] [PMID: 30810545]
[2]
Durazzo TC, Mattsson N, Weiner MW. Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms. Alzheimers Dement 2014; 10(3S): S122-45.
[http://dx.doi.org/10.1016/j.jalz.2014.04.009] [PMID: 24924665]
[3]
Jordan CJ, Xi Z-X. Discovery and development of varenicline for smoking cessation. Expert Opin Drug Discov 2018; 13(7): 671-83.
[4]
Hendrickson LM, Guildford MJ, Tapper AR. Neuronal nicotinic acetylcholine receptors: Common molecular substrates of nicotine and alcohol dependence. Front Psychiatry 2013; 4: 29.
[http://dx.doi.org/10.3389/fpsyt.2013.00029] [PMID: 23641218]
[5]
Le Novère N, Changeux JP. Molecular evolution of the nicotinic acetylcholine receptor: An example of multigene family in excitable cells. J Mol Evol 1995; 40(2): 155-72.
[http://dx.doi.org/10.1007/BF00167110] [PMID: 7699721]
[6]
Ho TNT, Abraham N, Lewis RJ. Structure-function of neuronal nicotinic acetylcholine receptor inhibitors derived from natural toxins. Front Neurosci 2020; 14: 609005.
[http://dx.doi.org/10.3389/fnins.2020.609005] [PMID: 33324158]
[7]
Albuquerque EX, Pereira EFR, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: From structure to function. Physiol Rev 2009; 89(1): 73-120.
[http://dx.doi.org/10.1152/physrev.00015.2008] [PMID: 19126755]
[8]
Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 2004; 12(6): 305-20.
[http://dx.doi.org/10.1080/10673220490910844] [PMID: 15764467]
[9]
Xiao C, Zhou C, Jiang J, Yin C. Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence. Acta Pharmacol Sin 2020; 41(1): 1-9.
[http://dx.doi.org/10.1038/s41401-019-0299-4] [PMID: 31554960]
[10]
Salloum NC, Buchalter ELF, Chanani S, et al. From genes to treatments: A systematic review of the pharmacogenetics in smoking cessation. Pharmacogenomics 2018; 19(10): 861-71.
[http://dx.doi.org/10.2217/pgs-2018-0023] [PMID: 29914292]
[11]
Bergen AW, Javitz HS, Krasnow R, et al. Nicotinic acetylcholine receptor variation and response to smoking cessation therapies. Pharmacogenet Genomics 2013; 23(2): 94-103.
[http://dx.doi.org/10.1097/FPC.0b013e32835cdabd] [PMID: 23249876]
[12]
Chen LS, Baker TB, Jorenby D, et al. Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation. Drug Alcohol Depend 2015; 154: 278-82.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.06.022] [PMID: 26142345]
[13]
Chen X, Chen J, Williamson VS, et al. Variants in nicotinic acetylcholine receptors α5 and α3 increase risks to nicotine dependence. Am J Med Genet B Neuropsychiatr Genet 2009; 150B(7): 926-33.
[http://dx.doi.org/10.1002/ajmg.b.30919] [PMID: 19132693]
[14]
Chen LS, Bloom AJ, Baker TB, et al. Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction 2014; 109(1): 128-37.
[http://dx.doi.org/10.1111/add.12353] [PMID: 24033696]
[15]
Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 2010; 42(5): 441-7.
[http://dx.doi.org/10.1038/ng.571] [PMID: 20418890]
[16]
Rocha Santos J, Tomaz PRX, Issa JS, et al. CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy. Front Genet 2015; 6: 46.
[http://dx.doi.org/10.3389/fgene.2015.00046] [PMID: 25774163]
[17]
Barr J, Sharma CS, Sarkar S, et al. Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells. Mol Cell Biochem 2007; 297(1-2): 93-9.
[http://dx.doi.org/10.1007/s11010-006-9333-1] [PMID: 17021677]
[18]
Anbarasi K, Vani G, Devi CSS. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats. J Environ Pathol Toxicol Oncol 2005; 24(3): 225-34.
[http://dx.doi.org/10.1615/JEnvPathToxOncol.v24.i3.80] [PMID: 16050806]
[19]
Rueff-Barroso CR, Trajano ET, Alves JN, et al. Organ-related cigarette smoke-induced oxidative stress is strain-dependent. Med Sci Monit 2010; 16(7): BR218-26.
[PMID: 20581770]
[20]
Nordberg A, Hellström-Lindahl E, Lee M, et al. Chronic nicotine treatment reduces β-amyloidosis in the brain of a mouse model of Alzheimer’s disease (APPsw). J Neurochem 2002; 81(3): 655-8.
[http://dx.doi.org/10.1046/j.1471-4159.2002.00874.x] [PMID: 12065674]
[21]
Echeverria V, Zeitlin R, Burgess S, et al. Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer’s disease mice. J Alzheimers Dis 2011; 24(4): 817-35.
[http://dx.doi.org/10.3233/JAD-2011-102136] [PMID: 21321389]
[22]
Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55(3): 306-19.
[http://dx.doi.org/10.1002/ana.20009] [PMID: 14991808]
[23]
Weng PH, Chen JH, Chen TF, et al. CHRNA7 polymorphisms and dementia risk: Interactions with apolipoprotein ε4 and cigarette smoking. Sci Rep 2016; 6(1): 27231.
[http://dx.doi.org/10.1038/srep27231] [PMID: 27249957]
[24]
Russo P, Kisialiou A, Moroni R, Prinzi G, Fini M. Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease. Curr Drug Targets 2017; 18(10): 1179-90.
[PMID: 26424395]
[25]
Weng PH, Chen JH, Chen TF, et al. CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer’s disease. PLoS One 2013; 8(12): e84059.
[http://dx.doi.org/10.1371/journal.pone.0084059] [PMID: 24391883]
[26]
Li MD, Cheng R, Ma JZ, Swan GE. A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins. Addiction 2003; 98(1): 23-31.
[http://dx.doi.org/10.1046/j.1360-0443.2003.00295.x] [PMID: 12492752]
[27]
Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 2007; 47(1): 699-729.
[http://dx.doi.org/10.1146/annurev.pharmtox.47.120505.105214] [PMID: 17009926]
[28]
Zhu H, Clemens S, Sawchuk M, Hochman S. Unaltered D1, D2, D4, and D5 dopamine receptor mRNA expression and distribution in the spinal cord of the D3 receptor knockout mouse. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2008; 194(11): 957-62.
[http://dx.doi.org/10.1007/s00359-008-0368-5] [PMID: 18797877]
[29]
Herman AI, DeVito EE, Jensen KP, Sofuoglu M. Pharmacogenetics of nicotine addiction: Role of dopamine. Pharmacogenomics 2014; 15(2): 221-34.
[http://dx.doi.org/10.2217/pgs.13.246] [PMID: 24444411]
[30]
Murphy M, Johnstone E, Griffiths S-E, et al. Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome? Nicotine Tob Res 2003; 5(6): 935-42.
[http://dx.doi.org/10.1080/14622200310001615295] [PMID: 14668077]
[31]
David SP, Strong DR, Munafò MR, et al. Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: analysis of pooled data from two clinical trials. Nicotine Tob Res 2007; 9(12): 1251-7.
[http://dx.doi.org/10.1080/14622200701705027] [PMID: 18058343]
[32]
Swan GE, Valdes AM, Ring HZ, et al. Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR. Pharmacogenomics J 2005; 5(1): 21-9.
[http://dx.doi.org/10.1038/sj.tpj.6500281] [PMID: 15492764]
[33]
Wang E, Ding YC, Flodman P, et al. The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. Am J Hum Genet 2004; 74(5): 931-44.
[http://dx.doi.org/10.1086/420854] [PMID: 15077199]
[34]
David SP, Munafò MR, Murphy M F G, Proctor M, Walton RT, Johnstone EC. Genetic variation in the dopamine D4 receptor (DRD4) gene and smoking cessation: Follow-up of a randomised clinical trial of transdermal nicotine patch. Pharmacogenomics J 2008; 8(2): 122-8.
[http://dx.doi.org/10.1038/sj.tpj.6500447] [PMID: 17387332]
[35]
Tomlinson G, Tsoh J, De Moor C, et al. The effects of the DRD2 polymorphism on smoking cessation and negative affect: Evidence for a pharmacogenetic effect on mood. Nicotine Tob Res 2004; 6(2): 229-39.
[http://dx.doi.org/10.1080/14622200410001676396] [PMID: 15203796]
[36]
Mill J, Asherson P, Browes C, D’Souza U, Craig I. Expression of the dopamine transporter gene is regulated by the 3? UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 2002; 114(8): 975-9.
[http://dx.doi.org/10.1002/ajmg.b.10948] [PMID: 12457396]
[37]
Berrettini WH, Wileyto EP, Epstein L, et al. Catechol-O-methyltransferase (COMT) gene variants predict response to bupropion therapy for tobacco dependence. Biol Psychiatry 2007; 61(1): 111-8.
[http://dx.doi.org/10.1016/j.biopsych.2006.04.030] [PMID: 16876132]
[38]
Johnstone EC, Yudkin PL, Hey K, et al. Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch. Pharmacogenetics 2004; 14(2): 83-90.
[http://dx.doi.org/10.1097/00008571-200402000-00002] [PMID: 15077009]
[39]
Ott T, Nieder A. Dopamine and cognitive control in prefrontal cortex. Trends Cogn Sci 2019; 23(3): 213-34.
[http://dx.doi.org/10.1016/j.tics.2018.12.006] [PMID: 30711326]
[40]
Westbrook A, Braver TS. Dopamine does double duty in motivating cognitive effort. Neuron 2016; 89(4): 695-710.
[http://dx.doi.org/10.1016/j.neuron.2015.12.029] [PMID: 26889810]
[41]
Jay TM. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog Neurobiol 2003; 69(6): 375-90.
[http://dx.doi.org/10.1016/S0301-0082(03)00085-6] [PMID: 12880632]
[42]
Axmacher N, Cohen MX, Fell J, et al. Intracranial EEG correlates of expectancy and memory formation in the human hippocampus and nucleus accumbens. Neuron 2010; 65(4): 541-9.
[http://dx.doi.org/10.1016/j.neuron.2010.02.006] [PMID: 20188658]
[43]
Lisman JE, Grace AA. The hippocampal-VTA loop: Controlling the entry of information into long-term memory. Neuron 2005; 46(5): 703-13.
[http://dx.doi.org/10.1016/j.neuron.2005.05.002] [PMID: 15924857]
[44]
Takahashi H, Kato M, Takano H, et al. Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. J Neurosci 2008; 28(46): 12032-8.
[http://dx.doi.org/10.1523/JNEUROSCI.3446-08.2008] [PMID: 19005068]
[45]
Castillo Díaz F, Caffino L, Fumagalli F. Bidirectional role of dopamine in learning and memory-active forgetting. Neurosci Biobehav Rev 2021; 131: 953-63.
[http://dx.doi.org/10.1016/j.neubiorev.2021.10.011] [PMID: 34655655]
[46]
Pan X, Kaminga AC, Wen SW, Wu X, Acheampong K, Liu A. Dopamine and dopamine receptors in alzheimer’s disease: A systematic review and network meta-analysis. Front Aging Neurosci 2019; 11: 175.
[http://dx.doi.org/10.3389/fnagi.2019.00175] [PMID: 31354471]
[47]
Nobili A, Latagliata EC, Viscomi MT, et al. Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease. Nat Commun 2017; 8(1): 14727.
[http://dx.doi.org/10.1038/ncomms14727] [PMID: 28367951]
[48]
Brenner DE, Kukull WA, van Belle G, et al. Relationship between cigarette smoking and Alzheimer’s disease in a population-based case-control study. Neurology 1993; 43(2): 293-300.
[http://dx.doi.org/10.1212/WNL.43.2.293] [PMID: 8437692]
[49]
Salib E, Hillier V. A case-control study of smoking and Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12(3): 295-300.
[http://dx.doi.org/10.1002/(SICI)1099-1166(199703)12:3<295:AID-GPS476>3.0.CO;2-3] [PMID: 9152711]
[50]
Cataldo JK, Prochaska JJ, Glantz SA. Cigarette smoking is a risk factor for Alzheimer’s Disease: An analysis controlling for tobacco industry affiliation. J Alzheimers Dis 2010; 19(2): 465-80.
[http://dx.doi.org/10.3233/JAD-2010-1240] [PMID: 20110594]
[51]
Almeida OP, Hulse GK, Lawrence D, Flicker L. Smoking as a risk factor for Alzheimer’s disease: Contrasting evidence from a systematic review of case-control and cohort studies. Addiction 2002; 97(1): 15-28.
[http://dx.doi.org/10.1046/j.1360-0443.2002.00016.x] [PMID: 11895267]
[52]
deBry S, Tiffany S. Tobacco-Induced Neurotoxicity Of Adolescent Cognitive Development (TINACD): A proposed model for the development of impulsivity in nicotine dependence. Nicotine Tob Res 2008; 10(1): 11-25.
[http://dx.doi.org/10.1080/14622200701767811] [PMID: 18188741]
[53]
Akkermans SEA, van Rooij D, Rommelse N, et al. Effect of tobacco smoking on frontal cortical thickness development: A longitudinal study in a mixed cohort of ADHD-affected and -unaffected youth. Eur Neuropsychopharmacol 2017; 27(10): 1022-31.
[http://dx.doi.org/10.1016/j.euroneuro.2017.07.007] [PMID: 28764867]
[54]
Durazzo TC, Meyerhoff DJ, Yoder KK. Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer’s Disease. Drug Alcohol Depend 2018; 192: 277-84.
[http://dx.doi.org/10.1016/j.drugalcdep.2018.08.009] [PMID: 30300802]
[55]
Karama S, Ducharme S, Corley J, et al. Cigarette smoking and thinning of the brain’s cortex. Mol Psychiatry 2015; 20(6): 778-85.
[http://dx.doi.org/10.1038/mp.2014.187] [PMID: 25666755]
[56]
Wang C, Zhou C, Guo T, Huang P, Xu X, Zhang M. Association between cigarette smoking and Parkinson’s disease: A neuroimaging study. Ther Adv Neurol Disord 2022; 15: 17562864221092566.
[http://dx.doi.org/10.1177/17562864221092566] [PMID: 35464739]
[57]
Alhowail A. Molecular insights into the benefits of nicotine on memory and cognition. Mol Med Rep 2021; 23(6): 398.
[http://dx.doi.org/10.3892/mmr.2021.12037] [PMID: 33786606]

Rights & Permissions Print Cite
Article Metrics
31
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy