尼古丁代谢相关细胞色素P450家族及其与帕金森病发病关系的研究进展
摘要
帕金森病(PD)是一种常见的神经系统退行性疾病,其发病病因及机制尚不明确,目前治疗方案仅可缓解症状,不能阻止疾病进展。多项国内外的回顾性及前瞻性研究表明,PD发病风险与日吸烟量、烟龄负相关。香烟内含有大量的尼古丁,与尼古丁代谢相关的CYP450家族成员主要有CYP2A6、CYP2B、CYP2D、CYP2E1。CYP2A6基因可促进尼古丁的代谢,尼古丁可使脑组织中CYP2B6、CYP2D升高、CYP2E1酶活性增强。尼古丁可通过CYP450对受损的多巴胺能神经元起保护作用,从而预防PD发病。
引文
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[2]Searles NS,Gallagher LG,Lundin JI,et al. Environmental tobacco smoke and Parkinson's disease[J]. Movement Disorders,2012,27(2):293-296.
[3]Smith CA,Gough AC,Leigh PN,et al. Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease[J].Lancet,1992,339(8806):1375-1377.
[4]Tanner JA,Tyndale RF. Variation in CYP2A6 activity and personalized medicine[J]. J Pers Med,2017,7(4):18.
[5]Garcia KL,Coen K,Miksys S,et al. Effect of Brain CYP2B inhibition on brain nicotine levels and nicotine self-administration[J].Neuropsych-opharmacology,2015,40(8):1910-1918.
[6]Miller RT,Miksys S,Hoffmann E,et al. Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys[J]. Br J Pharmacol,2014,171(12):3077-3088.
[7]Ferguson CS,Miksys S,Palmour RM,et al. Ethanol self-administration and nicotine treatment induce brain levels of CYP2B6 and CYP2E1 in African green monkeys[J]. Neuropharmacology,2013,72:74-81.
[8]Ladda MA,Goralski KB. The effects of ckd on cytochrome P450-mediated drug metabolism[J]. Adv Chronic Kidney Dis,2016,23(2):67-75.
[9] Wassenaar CA,Dong Q,Wei Q,et al. Relationship between CYP2A6 and CHRNA5-CHRNA3-CHRNB4 variation and smoking behaviors and lung cancer risk[J]. J Natl Cancer Inst,2011,103(17):1342-1346.
[10]Bloom J,Hinrichs AL,Wang JC,et al. The contribution of common CYP2A6 alleles to variation in nicotine metabolism among European-Americans[J]. Pharmacogenet Genomics,2011,21(7):403-416.
[11]Yuan JM,Nelson HH,Butler LM,et al. Genetic determinants of cytochrome P450 2A6 activity and biomarkers of tobacco smoke exposure in relation to risk of lung cancer development in the Shanghai cohort study[J]. Int J Cancer,2016,138(9):2161-2171.
[12]Turpeinen M,Zanger UM. Cytochrome P450 2B6:function,genetics,and clinical relevance[J]. Drug Metabol Drug Interact,2012,27(4):185-197.
[13]Lee AM,Jepson C,Shields PG,et al. CYP2B6 genotype does not alter nicotine metabolism,plasma levels,or abstinence with nicotine replacement therapy[J]. Cancer Epidemiol Biomarkers Prev,2007,16(6):1312-1314.
[14]Ring HZ,Valdes AM,Nishita DM,et al. Gene-gene interactions between CYP2B6 and CYP2A6 in nicotine metabolism[J]. Pharmacogenet Genomics,2007,17(12):1007-1015.
[15]Miksys S,Tyndale RF. The unique regulation of brain cytochrome P4502(CYP2)family enzymes by drugs and genetics[J]. Drug Metab Rev,2004,36(2):313-333.
[16] Ferguson CS,Tyndale RF. Cytochrome P450 enzymes in the brain:emerging evidence of biological significance[J]. Trends Pharmacol Sci,2011,32(12):708-714.
[17]Yue J,Miksys S,Hoffmann E,et al. Chronic nicotine treatment induces rat CYP2D in the brain but not in the liver:an investigation of induction and time course[J]. J Psychiatry Neurosci,2008,33(1):54-63.
[18]Ritz B,Ascherio A,Checkoway H,et al. Pooled analysis of tobacco use and risk of Parkinson disease[J]. Arch Neurol,2007,64(7):990-997.
[19] Chen H,Huang X,Guo X,et al. Smoking duration,intensity,and risk of Parkinson disease[J]. Neurology,2010,74(11):878-884.
[20]Leino S,Koski SK,Rannanp S,et al. Effects of antidyskinetic nicotine treatment on dopamine release in dorsal and ventral striatum[J]. Neurosci Lett,2018,672:40-45.
[21]Grady SR,Salminen O,Laverty DC,et al. The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum[J]. Biochem Pharmacol,2007,74(8):1235-1246.
[22]Srinivasan R,Henley BM,Henderson BJ,et al. Smoking-relevant nicotine concentration attenuates the unfolded protein response in dopaminergic neurons[J]. J Neurosci,2016,36(1):65-79.
[23]Liu Y,Zeng X,Hui Y,et al. Activation ofα7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis:implications for Parkinson's disease[J]. Neuropharmacology,2015,91:87-96.
[24]Mouhape C,Costa G,Ferreira M,et al. Nicotine-induced neuroprotection in rotenone in vivo and in vitro models of parkinson’s disease:evidences for the involvement of the labile iron pool level as the underlying mechanism[J]. Neurotox Res,2019,35(1):71-82.
[25]Gigante AF,Asabella AN,Iliceto G,et al. Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's disease[J]. Neurol Sci,2018,39(3):551-555.
[26]Haduch A,Bromek E,Daniel WA. Role of brain cytochrome P450(CYP2D)in the metabolism of monoaminergic neurotransmitters[J]. Pharmacol Rep,2013,65(6):1519-1528.
[27]Lu Y,Peng Q,Zeng Z,et al. CYP2D6 phenotypes and Parkinson's disease risk:a meta-analysis[J]. J Neurol Sci,2014,336(1-2):161-168.
[28]Mann A,Tyndale RF. Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronalcells[J]. Eur J Neurosci,2010,31(7):1185-1193.
[29] Viaggi C,Vaglini F,Pardini C,et al. MPTP-induced model of Parkinson's disease in cytochrome P450 2E1knockout mice[J].Neuropharmacology,2009,56(8):1075-1081.
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