Plant Polyphenols as Neuroprotective Agents in Parkinson’s Disease Targeting Oxidative Stress

doi:10.2174/1389450120666191017120505
摘要

帕金森氏病（PD）是第二大最普遍的进行性神经退行性疾病，其特征是人中脑中的多巴胺能神经元变性。正在进行的各种研究竞赛正在竞争以了解PD的病理学并阐明神经退行性病变的机制。尽管长期使用有副作用，但目前的药物治疗主要集中在改善PD患者的多巴胺代谢上。近年来，已经认识到氧化应激介导的途径导致脑中神经变性，这与PD的病理生理学有关。在开发潜在的治疗方法时，常常不会强调氧化应激的重要性。天然植物抗氧化剂已显示出介导PD中氧化应激诱导的作用，在体外和体内研究中都引起了广泛关注。然而，关于天然多酚化合物的临床试验是有限的，限制了这些化合物作为PD替代疗法的潜在用途。因此，本综述通过阐明促成氧化应激的潜在事件，并了解了多酚在改善PD氧化状态中的潜在用途，从而了解了PD中氧化应激诱导的作用。临床前研究结果支持了多酚在针对PD的氧化应激诱导的毒性提供神经保护方面的潜力。但是，限制因素，例如多酚的安全性和生物利用度，值得进一步研究，以使其成为PD治疗和管理中临床应用的潜在目标。
关键词: 抗氧化剂，帕金森氏病，多酚，氧化应激，神经保护，生物利用度。
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图形摘要

[1] 
Dexter DT, Jenner P. Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med  2013; 62: 132-44.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.018] [PMID:  23380027] 
[2] 
Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord  2014; 29(13): 1583-90.
[http://dx.doi.org/10.1002/mds.25945] [PMID:  24976103] 
[3] 
Obeso JA, Rodriguez-Oroz MC, Goetz CG, et al. Missing pieces in the Parkinson’s disease puzzle. Nat Med  2010; 16(6): 653-61.
[http://dx.doi.org/10.1038/nm.2165] [PMID:  20495568] 
[4] 
Baradaran N, Tan SN, Liu A, et al. Parkinson’s disease rigidity: relation to brain connectivity and motor performance. Front Neurol  2013; 4: 67.
[http://dx.doi.org/10.3389/fneur.2013.00067] [PMID:  23761780] 
[5] 
Vervoort G, Bengevoord A, Nackaerts E, Heremans E, Vandenberghe W, Nieuwboer A. Distal motor deficit contributions to postural instability and gait disorder in Parkinson’s disease. Behav Brain Res  2015; 287: 1-7.
[http://dx.doi.org/10.1016/j.bbr.2015.03.026] [PMID:  25804361] 
[6] 
Chaudhuri KR, Schapira AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol  2009; 8(5): 464-74.
[http://dx.doi.org/10.1016/S1474-4422(09)70068-7] [PMID:  19375664] 
[7] 
Kalia LV, Lang AE. Parkinson’s disease. Lancet  2015; 386(9996): 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID:  25904081] 
[8] 
Plowman EK, Kleim JA. Behavioral and neurophysiological correlates of striatal dopamine depletion: a rodent model of Parkinson’s disease. J Commun Disord  2011; 44(5): 549-56.
[http://dx.doi.org/10.1016/j.jcomdis.2011.04.008] [PMID:  21601869] 
[9] 
Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol  2009; 8(12): 1150-7.
[http://dx.doi.org/10.1016/S1474-4422(09)70238-8] [PMID:  19909913] 
[10] 
Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci  2011; 34: 441-66.
[http://dx.doi.org/10.1146/annurev-neuro-061010-113641] [PMID:  21469956] 
[11] 
Luk KC, Kehm V, Carroll J, et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science  2012; 338(6109): 949-53.
[http://dx.doi.org/10.1126/science.1227157] [PMID:  23161999] 
[12] 
Del Tredici K, Duda JE. Peripheral Lewy body pathology in Parkinson’s disease and incidental Lewy body disease: four cases. J Neurol Sci  2011; 310(1-2): 100-6.
[http://dx.doi.org/10.1016/j.jns.2011.06.003] [PMID:  21689832] 
[13] 
Tong J, Wong H, Guttman M, et al. Brain alpha-synuclein accumulation in multiple system atrophy, Parkinson’s disease and progressive supranuclear palsy: a comparative investigation. Brain  2010; 133(Pt 1): 172-88.
[http://dx.doi.org/10.1093/brain/awp282] [PMID:  19903734] 
[14] 
Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci  2005; 28: 57-87.
[http://dx.doi.org/10.1146/annurev.neuro.28.061604.135718] [PMID:  16022590] 
[15] 
Büeler H. Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson’s disease. Exp Neurol  2009; 218(2): 235-46.
[http://dx.doi.org/10.1016/j.expneurol.2009.03.006] [PMID:  19303005] 
[16] 
Thomas B, Beal MF. Molecular insights into Parkinson’s disease. F1000 Med Rep  2011; 3: 7.
[http://dx.doi.org/10.3410/M3-7] [PMID:  21655332] 
[17] 
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ. The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology  1998; 50(5): 1346-50.
[http://dx.doi.org/10.1212/WNL.50.5.1346] [PMID:  9595985] 
[18] 
Schapira AH, Jenner P. Etiology and pathogenesis of Parkinson’s disease. Mov Disord  2011; 26(6): 1049-55.
[http://dx.doi.org/10.1002/mds.23732] [PMID:  21626550] 
[19] 
Noyce AJ, Bestwick JP, Silveira-Moriyama L, et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol  2012; 72(6): 893-901.
[http://dx.doi.org/10.1002/ana.23687] [PMID:  23071076] 
[20] 
Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science  1983; 219(4587): 979-80.
[http://dx.doi.org/10.1126/science.6823561] [PMID:  6823561] 
[21] 
Tanner CM, Kamel F, Ross GW, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect  2011; 119(6): 866-72.
[http://dx.doi.org/10.1289/ehp.1002839] [PMID:  21269927] 
[22] 
Silva BA, Breydo L, Fink AL, Uversky VN. Agrochemicals, α-synuclein, and Parkinson’s disease. Mol Neurobiol  2013; 47(2): 598-612.
[http://dx.doi.org/10.1007/s12035-012-8333-2] [PMID:  22933040] 
[23] 
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci  2000; 3(12): 1301-6.
[http://dx.doi.org/10.1038/81834] [PMID:  11100151] 
[24] 
Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis  2009; 34(2): 279-90.
[http://dx.doi.org/10.1016/j.nbd.2009.01.016] [PMID:  19385059] 
[25] 
Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener  2017; 12(1): 10.
[http://dx.doi.org/10.1186/s13024-017-0149-0] [PMID:  28118852] 
[26] 
Jalewa J, Sharma MK, Hölscher C. Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells. J Neurochem  2016; 139(1): 55-67.
[http://dx.doi.org/10.1111/jnc.13736] [PMID:  27412483] 
[27] 
Katzenschlager R, Lees AJ. Treatment of Parkinson’s disease: levodopa as the first choice. J Neurol  2002; 249(Suppl. 2): II19-24.
[http://dx.doi.org/10.1007/s00415-002-1204-4] [PMID:  12375059] 
[28] 
Hornykiewicz O. A brief history of levodopa. J Neurol  2010; 257(Suppl. 2): S249-52.
[http://dx.doi.org/10.1007/s00415-010-5741-y] [PMID:  21080185] 
[29] 
Mallajosyula JK, Kaur D, Chinta SJ, et al. MAO-B elevation in mouse brain astrocytes results in Parkinson’s pathology. PLoS One  2008; 3(2)e1616
[http://dx.doi.org/10.1371/journal.pone.0001616] [PMID:  18286173] 
[30] 
Simola N. Emerging drugs and targets for Parkinson’s disease.  Cambridge: Royal Society of Chemistry 2014; pp. 61-82.
[31] 
Szökő É, Tábi T, Riederer P, Vécsei L, Magyar K. Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease. J Neural Transm (Vienna)  2018; 125(11): 1735-49.
[http://dx.doi.org/10.1007/s00702-018-1853-9] [PMID:  29417334] 
[32] 
Cools R, Barker RA, Sahakian BJ, Robbins TW. L-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease. Neuropsychologia  2003; 41(11): 1431-41.
[http://dx.doi.org/10.1016/S0028-3932(03)00117-9] [PMID:  12849761] 
[33] 
Ito D, Amano T, Sato H, Fukuuchi Y. Paroxysmal hypertensive crises induced by selegiline in a patient with Parkinson’s disease. J Neurol  2001; 248(6): 533-4.
[http://dx.doi.org/10.1007/s004150170168] [PMID:  11499649] 
[34] 
Li BD, Bi ZY, Liu JF, et al. Adverse effects produced by different drugs used in the treatment of Parkinson’s disease: A mixed treatment comparison. CNS Neurosci Ther  2017; 23(10): 827-42.
[http://dx.doi.org/10.1111/cns.12727] [PMID:  28872217] 
[35] 
Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med  2000; 342(20): 1484-91.
[http://dx.doi.org/10.1056/NEJM200005183422004] [PMID:  10816186] 
[36] 
Fedorova T, Logvinenko A, Poleshchuk V, Illarioshkin S. The state of systemic oxidative stress during Parkinson’s disease. Neurochem J  2017; 11: 340-5.
[http://dx.doi.org/10.1134/S1819712417040031] 
[37] 
Hwang O. Role of oxidative stress in Parkinson’s disease. Exp Neurobiol  2013; 22(1): 11-7.
[http://dx.doi.org/10.5607/en.2013.22.1.11] [PMID:  23585717] 
[38] 
Di Matteo V, Esposito E. Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Curr Drug Targets CNS Neurol Disord  2003; 2(2): 95-107.
[http://dx.doi.org/10.2174/1568007033482959] [PMID:  12769802] 
[39] 
Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol  2009; 7(1): 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID:  19721819] 
[40] 
Almeida S, Alves MG, Sousa M, Oliveira PF, Silva BM. Are polyphenols strong dietary agents against neurotoxicity and neurodegeneration? Neurotox Res  2016; 30(3): 345-66.
[http://dx.doi.org/10.1007/s12640-015-9590-4] [PMID:  26745969] 
[41] 
Pohl F, Kong Thoo Lin P. The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: in vitro, in vivo and clinical trials. Molecules  2018; 23(12): 23.
[http://dx.doi.org/10.3390/molecules23123283] [PMID:  30544977] 
[42] 
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev  2009; 2(5): 270-8.
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID:  20716914] 
[43] 
Melo A, Monteiro L, Lima RM, Oliveira DM, Cerqueira MD, El-Bachá RS. Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives. Oxid Med Cell Longev 2011.2011467180
[http://dx.doi.org/10.1155/2011/467180] [PMID:  22191013] 
[44] 
Jellinger KA. Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med  2010; 14(3): 457-87.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01010.x] [PMID:  20070435] 
[45] 
Valencia A, Morán J. Reactive oxygen species induce different cell death mechanisms in cultured neurons. Free Radic Biol Med  2004; 36(9): 1112-25.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.02.013] [PMID:  15082065] 
[46] 
Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis  2013; 3(4): 461-91.
[PMID:  24252804] 
[47] 
Kobayashi H, Fukuhara K, Tada-Oikawa S, et al. The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson’s disease. J Neurochem  2009; 108(2): 397-407.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05774.x] [PMID:  19012744] 
[48] 
Goodwin J, Nath S, Engelborghs Y, Pountney DL. Raised calcium and oxidative stress cooperatively promote alpha-synuclein aggregate formation. Neurochem Int  2013; 62(5): 703-11.
[http://dx.doi.org/10.1016/j.neuint.2012.11.004] [PMID:  23159813] 
[49] 
Sanders LH, Timothy Greenamyre J. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol Med  2013; 62: 111-20.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.003] [PMID:  23328732] 
[50] 
Garbarino VR, Orr ME, Rodriguez KA, Buffenstein R. Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates. Arch Biochem Biophys  2015; 576: 8-16.
[http://dx.doi.org/10.1016/j.abb.2015.01.029] [PMID:  25841340] 
[51] 
Duan W, Zhu X, Ladenheim B, et al. p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism. Ann Neurol  2002; 52(5): 597-606.
[http://dx.doi.org/10.1002/ana.10350] [PMID:  12402257] 
[52] 
Herbin M, Simonis C, Revéret L, et al. Dopamine modulates motor control in a specific plane related to support. PLoS One  2016; 11(5)e0155058
[http://dx.doi.org/10.1371/journal.pone.0155058] [PMID:  27145032] 
[53] 
Ershov PV, Ugrumov MV, Calas A, Makarenko IG, Krieger M, Thibault J. Neurons possessing enzymes of dopamine synthesis in the mediobasal hypothalamus of rats. Topographic relations and axonal projections to the median eminence in ontogenesis. J Chem Neuroanat  2002; 24(2): 95-107.
[http://dx.doi.org/10.1016/S0891-0618(02)00019-4] [PMID:  12191726] 
[54] 
Nirenberg MJ, Chan J, Liu Y, Edwards RH, Pickel VM. Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: potential sites for somatodendritic storage and release of dopamine. J Neurosci  1996; 16(13): 4135-45.
[http://dx.doi.org/10.1523/JNEUROSCI.16-13-04135.1996] [PMID:  8753875] 
[55] 
Asanuma M, Miyazaki I, Ogawa N. Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res  2003; 5(3): 165-76.
[http://dx.doi.org/10.1007/BF03033137] [PMID:  12835121] 
[56] 
Vergo S, Johansen JL, Leist M, Lotharius J. Vesicular monoamine transporter 2 regulates the sensitivity of rat dopaminergic neurons to disturbed cytosolic dopamine levels. Brain Res  2007; 1185: 18-32.
[http://dx.doi.org/10.1016/j.brainres.2007.09.028] [PMID:  18028884] 
[57] 
Chen L, Ding Y, Cagniard B, et al. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci  2008; 28(2): 425-33.
[http://dx.doi.org/10.1523/JNEUROSCI.3602-07.2008] [PMID:  18184785] 
[58] 
Caudle WM, Richardson JR, Wang MZ, et al. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci  2007; 27(30): 8138-48.
[http://dx.doi.org/10.1523/JNEUROSCI.0319-07.2007] [PMID:  17652604] 
[59] 
Mukda S, Vimolratana O, Govitrapong P. Melatonin attenuates the amphetamine-induced decrease in vesicular monoamine transporter-2 expression in postnatal rat striatum. Neurosci Lett  2011; 488(2): 154-7.
[http://dx.doi.org/10.1016/j.neulet.2010.11.019] [PMID:  21078367] 
[60] 
Wasik A, Romańska I, Antkiewicz-Michaluk L. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous parkinsonism-inducing toxin, strongly potentiates MAO-dependent dopamine oxidation and impairs dopamine release: ex vivo and in vivo neurochemical studies. Neurotox Res  2009; 15(1): 15-23.
[http://dx.doi.org/10.1007/s12640-009-9001-9] [PMID:  19384584] 
[61] 
Uhl GR, Li S, Takahashi N, et al. The VMAT2 gene in mice and humans: amphetamine responses, locomotion, cardiac arrhythmias, aging, and vulnerability to dopaminergic toxins. FASEB J  2000; 14(15): 2459-65.
[http://dx.doi.org/10.1096/fj.00-0205rev] [PMID:  11099463] 
[62] 
Pifl C, Rajput A, Reither H, et al. Is Parkinson’s disease a vesicular dopamine storage disorder? Evidence from a study in isolated synaptic vesicles of human and nonhuman primate striatum. J Neurosci  2014; 34(24): 8210-8.
[http://dx.doi.org/10.1523/JNEUROSCI.5456-13.2014] [PMID:  24920625] 
[63] 
Basma AN, Morris EJ, Nicklas WJ, Geller HM. L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation. J Neurochem  1995; 64(2): 825-32.
[http://dx.doi.org/10.1046/j.1471-4159.1995.64020825.x] [PMID:  7830076] 
[64] 
Jinsmaa Y, Florang VR, Rees JN, et al. Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson’s disease. Chem Biol Interact  2011; 192(1-2): 118-21.
[http://dx.doi.org/10.1016/j.cbi.2011.01.006] [PMID:  21238438] 
[65] 
Doorn JA, Florang VR, Schamp JH, Vanle BC. Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons. Parkinsonism Relat Disord  2014; 20(Suppl. 1): S73-5.
[http://dx.doi.org/10.1016/S1353-8020(13)70019-1] [PMID:  24262193] 
[66] 
Cohen G. Oxidative stress, mitochondrial respiration, and Parkinson’s disease. Ann N Y Acad Sci  2000; 899: 112-20.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06180.x] [PMID:  10863533] 
[67] 
Anderson DG, Mariappan SV, Buettner GR, Doorn JA. Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone. J Biol Chem  2011; 286(30): 26978-86.
[http://dx.doi.org/10.1074/jbc.M111.249532] [PMID:  21642436] 
[68] 
Rabinovic AD, Lewis DA, Hastings TG. Role of oxidative changes in the degeneration of dopamine terminals after injection of neurotoxic levels of dopamine. Neuroscience  2000; 101(1): 67-76.
[http://dx.doi.org/10.1016/S0306-4522(00)00293-1] [PMID:  11068137] 
[69] 
Müller T, Muhlack S. Cysteinyl-glycine reduction as marker for levodopa-induced oxidative stress in Parkinson’s disease patients. Mov Disord  2011; 26(3): 543-6.
[http://dx.doi.org/10.1002/mds.23384] [PMID:  21462263] 
[70] 
Post MR, Lieberman OJ, Mosharov EV. Can interactions between α-synuclein, dopamine and calcium explain selective neurodegeneration in Parkinson’s Disease? Front Neurosci  2018; 12: 161.
[http://dx.doi.org/10.3389/fnins.2018.00161] [PMID:  29593491] 
[71] 
Sulzer D, Zecca L. Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res  2000; 1(3): 181-95.
[http://dx.doi.org/10.1007/BF03033289] [PMID:  12835101] 
[72] 
Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med  2012; 366(4): 348-59.
[http://dx.doi.org/10.1056/NEJMra1004967] [PMID:  22276824] 
[73] 
Beard J. Iron deficiency alters brain development and functioning. J Nutr  2003; 133(5)(Suppl. 1): 1468S-72S.
[http://dx.doi.org/10.1093/jn/133.5.1468S] [PMID:  12730445] 
[74] 
Unger EL, Wiesinger JA, Hao L, Beard JL. Dopamine D2 receptor expression is altered by changes in cellular iron levels in PC12 cells and rat brain tissue. J Nutr  2008; 138(12): 2487-94.
[http://dx.doi.org/10.3945/jn.108.095224] [PMID:  19022977] 
[75] 
Wilkinson N, Pantopoulos K. The IRP/IRE system in vivo: insights from mouse models. Front Pharmacol  2014; 5: 176.
[http://dx.doi.org/10.3389/fphar.2014.00176] [PMID:  25120486] 
[76] 
Mills E, Dong XP, Wang F, Xu H. Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders. Future Med Chem  2010; 2(1): 51-64.
[http://dx.doi.org/10.4155/fmc.09.140] [PMID:  20161623] 
[77] 
Haacke EM, Cheng NYC, House MJ, et al. Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging  2005; 23(1): 1-25.
[http://dx.doi.org/10.1016/j.mri.2004.10.001] [PMID:  15733784] 
[78] 
Sian-Hülsmann J, Mandel S, Youdim MB, Riederer P. The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem  2011; 118(6): 939-57.
[http://dx.doi.org/10.1111/j.1471-4159.2010.07132.x] [PMID:  21138437] 
[79] 
Dexter DT, Carayon A, Javoy-Agid F, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain  1991; 114(Pt 4): 1953-75.
[http://dx.doi.org/10.1093/brain/114.4.1953] [PMID:  1832073] 
[80] 
Morawski M, Meinecke C, Reinert T, et al. Determination of trace elements in the human substantia nigra. Nucl Instrum Methods Phys Res B  2005; 231: 224-8.
[http://dx.doi.org/10.1016/j.nimb.2005.01.061] 
[81] 
Kaur D, Yantiri F, Rajagopalan S, et al. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson’s disease. Neuron  2003; 37(6): 899-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00126-0] [PMID:  12670420] 
[82] 
 Youdim MBH, Fridkin M, Zheng H. Novel bifunctional drugs
targeting monoamine oxidase inhibition and iron chelation as an
approach to neuroprotection in Parkinson’s disease and other neurodegenerative
diseases. Basic neurosciences and genetics, Parkinson's
disease and allied conditions, Alzheimer's disease and related
disorders, biological psychiatry. 2004; 111: 1455-71
[83] 
Ayton S, Lei P, Adlard PA, et al. Iron accumulation confers neurotoxicity to a vulnerable population of nigral neurons: implications for Parkinson’s disease. Mol Neurodegener  2014; 9: 27.
[http://dx.doi.org/10.1186/1750-1326-9-27] [PMID:  25011704] 
[84] 
Weinreb O, Mandel S, Youdim MBH, Amit T. Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Free Radic Biol Med  2013; 62: 52-64.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.01.017] [PMID:  23376471] 
[85] 
Lee DW, Andersen JK. Iron elevations in the aging Parkinsonian brain: a consequence of impaired iron homeostasis? J Neurochem  2010; 112(2): 332-9.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06470.x] [PMID:  20085612] 
[86] 
Carroll CB, Zeissler ML, Chadborn N, et al. Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson’s disease. Neurochem Int  2011; 59(1): 73-80.
[http://dx.doi.org/10.1016/j.neuint.2011.05.006] [PMID:  21672570] 
[87] 
Kalivendi SV, Kotamraju S, Cunningham S, Shang T, Hillard CJ, Kalyanaraman B. 1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide. Biochem J  2003; 371(Pt 1): 151-64.
[http://dx.doi.org/10.1042/bj20021525] [PMID:  12523938] 
[88] 
Bokare AD, Choi W. Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation processes. J Hazard Mater  2014; 275: 121-35.
[http://dx.doi.org/10.1016/j.jhazmat.2014.04.054] [PMID:  24857896] 
[89] 
LaVaute T, Smith S, Cooperman S, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet  2001; 27(2): 209-14.
[http://dx.doi.org/10.1038/84859] [PMID:  11175792] 
[90] 
Salvatore MF, Fisher B, Surgener SP, Gerhardt GA, Rouault T. Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Brain Res Mol Brain Res  2005; 139(2): 341-7.
[http://dx.doi.org/10.1016/j.molbrainres.2005.06.002] [PMID:  16051392] 
[91] 
Febbraro F, Giorgi M, Caldarola S, Loreni F, Romero-Ramos M. α-Synuclein expression is modulated at the translational level by iron. Neuroreport  2012; 23(9): 576-80.
[http://dx.doi.org/10.1097/WNR.0b013e328354a1f0] [PMID:  22581044] 
[92] 
Zhou ZD, Tan EK. Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases. Mol Neurodegener  2017; 12(1): 75.
[http://dx.doi.org/10.1186/s13024-017-0218-4] [PMID:  29061112] 
[93] 
Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014.2014360438
[http://dx.doi.org/10.1155/2014/360438] [PMID:  24999379] 
[94] 
Sánchez Campos S, Rodríguez Diez G, Oresti GM, Salvador GA. Dopaminergic neurons respond to iron-induced oxidative stress by modulating lipid acylation and deacylation cycles. PLoS One  2015; 10(6)e0130726
[http://dx.doi.org/10.1371/journal.pone.0130726] [PMID:  26076361] 
[95] 
Bertrand RL. Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events. Med Hypotheses  2017; 101: 69-74.
[http://dx.doi.org/10.1016/j.mehy.2017.02.017] [PMID:  28351498] 
[96] 
Shamoto-Nagai M, Maruyama W, Akao Y, et al. Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells. J Neural Transm (Vienna)  2004; 111(10-11): 1253-65.
[http://dx.doi.org/10.1007/s00702-004-0211-2] [PMID:  15480837] 
[97] 
Shamoto-Nagai M, Maruyama W, Hashizume Y, et al. In parkinsonian substantia nigra, α-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity. J Neural Transm (Vienna)  2007; 114(12): 1559-67.
[http://dx.doi.org/10.1007/s00702-007-0789-2] [PMID:  17690948] 
[98] 
Uversky VN, Li J, Fink AL. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson’s disease and heavy metal exposure. J Biol Chem  2001; 276(47): 44284-96.
[http://dx.doi.org/10.1074/jbc.M105343200] [PMID:  11553618] 
[99] 
Marengo B, Nitti M, Furfaro AL, et al. Redox homeostasis and cellular antioxidant systems: crucial players in cancer growth and therapy. Oxid Med Cell Longev 2016.20166235641
[http://dx.doi.org/10.1155/2016/6235641] [PMID:  27418953] 
[100] 
Kim GH, Kim JE, Rhie SJ, Yoon S. The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol  2015; 24(4): 325-40.
[http://dx.doi.org/10.5607/en.2015.24.4.325] [PMID:  26713080] 
[101] 
He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants. Cell Physiol Biochem  2017; 44(2): 532-53.
[http://dx.doi.org/10.1159/000485089] [PMID:  29145191] 
[102] 
Aoyama K, Watabe M, Nakaki T. Regulation of neuronal glutathione synthesis. J Pharmacol Sci  2008; 108(3): 227-38.
[http://dx.doi.org/10.1254/jphs.08R01CR] [PMID:  19008644] 
[103] 
Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med  2013; 62: 13-25.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.001] [PMID:  23665395] 
[104] 
Commandeur JN, Stijntjes GJ, Vermeulen NP. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of xenobiotics. Pharmacol Rev  1995; 47(2): 271-330.
[PMID:  7568330] 
[105] 
Sian J, Dexter DT, Lees AJ, et al. Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol  1994; 36(3): 348-55.
[http://dx.doi.org/10.1002/ana.410360305] [PMID:  8080242] 
[106] 
Pearce R, Owen A, Daniel S, Jenner P, Marsden C. Alterations in
the distribution of glutathione in the substantia nigra in Parkinson's
disease. Basic neurosciences and genetics, Parkinson's disease and
allied conditions, Alzheimer's disease and related disorders, biological
psychiatry. 1997; 104: 661-77. 
[http://dx.doi.org/10.1007/BF01291884] 
[107] 
Chinta SJ, Kumar MJ, Hsu M, et al. Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration. J Neurosci  2007; 27(51): 13997-4006.
[http://dx.doi.org/10.1523/JNEUROSCI.3885-07.2007] [PMID:  18094238] 
[108] 
Garrido M, Tereshchenko Y, Zhevtsova Z, Taschenberger G, Bähr M, Kügler S. Glutathione depletion and overproduction both initiate degeneration of nigral dopaminergic neurons. Acta Neuropathol  2011; 121(4): 475-85.
[http://dx.doi.org/10.1007/s00401-010-0791-x] [PMID:  21191602] 
[109] 
Mythri RB, Venkateshappa C, Harish G, et al. Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson’s disease brains. Neurochem Res  2011; 36(8): 1452-63.
[http://dx.doi.org/10.1007/s11064-011-0471-9] [PMID:  21484266] 
[110] 
Venkateshappa C, Harish G, Mythri RB, Mahadevan A, Bharath MM, Shankar SK. Increased oxidative damage and decreased antioxidant function in aging human substantia nigra compared to striatum: implications for Parkinson’s disease. Neurochem Res  2012; 37(2): 358-69.
[http://dx.doi.org/10.1007/s11064-011-0619-7] [PMID:  21971758] 
[111] 
Ramsey CP, Glass CA, Montgomery MB, et al. Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol  2007; 66(1): 75-85.
[http://dx.doi.org/10.1097/nen.0b013e31802d6da9] [PMID:  17204939] 
[112] 
Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med  2011; 32(4-6): 234-46.
[http://dx.doi.org/10.1016/j.mam.2011.10.006] [PMID:  22020111] 
[113] 
de Vries HE, Witte M, Hondius D, et al. Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med  2008; 45(10): 1375-83.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.09.001] [PMID:  18824091] 
[114] 
Lastres-Becker I, Ulusoy A, Innamorato NG, et al. α-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson’s disease. Hum Mol Genet  2012; 21(14): 3173-92.
[http://dx.doi.org/10.1093/hmg/dds143] [PMID:  22513881] 
[115] 
Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol  2003; 552(Pt 2): 335-44.
[http://dx.doi.org/10.1113/jphysiol.2003.049478] [PMID:  14561818] 
[116] 
Murphy MP. How mitochondria produce reactive oxygen species. Biochem J  2009; 417(1): 1-13.
[http://dx.doi.org/10.1042/BJ20081386] [PMID:  19061483] 
[117] 
Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol  2013; 106-107: 17-32.
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.004] [PMID:  23643800] 
[118] 
Hauser DN, Hastings TG. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease and monogenic parkinsonism. Neurobiol Dis  2013; 51: 35-42.
[http://dx.doi.org/10.1016/j.nbd.2012.10.011] [PMID:  23064436] 
[119] 
Mann VM, Cooper JM, Daniel SE, et al. Complex I, iron, and ferritin in Parkinson’s disease substantia nigra. Ann Neurol  1994; 36(6): 876-81.
[http://dx.doi.org/10.1002/ana.410360612] [PMID:  7998774] 
[120] 
Parker WD Jr, Parks JK, Swerdlow RH. Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res  2008; 1189: 215-8.
[http://dx.doi.org/10.1016/j.brainres.2007.10.061] [PMID:  18061150] 
[121] 
Valsecchi F, Koopman WJ, Manjeri GR, Rodenburg RJ, Smeitink JA, Willems PH. Complex I disorders: causes, mechanisms, and development of treatment strategies at the cellular level. Dev Disabil Res Rev  2010; 16(2): 175-82.
[http://dx.doi.org/10.1002/ddrr.107] [PMID:  20818732] 
[122] 
Li N, Ragheb K, Lawler G, et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem  2003; 278(10): 8516-25.
[http://dx.doi.org/10.1074/jbc.M210432200] [PMID:  12496265] 
[123] 
Przedborski S, Tieu K, Perier C, Vila M. MPTP as a mitochondrial neurotoxic model of Parkinson’s disease. J Bioenerg Biomembr  2004; 36(4): 375-9.
[http://dx.doi.org/10.1023/B:JOBB.0000041771.66775.d5] [PMID:  15377875] 
[124] 
Dranka BP, Zielonka J, Kanthasamy AG, Kalyanaraman B. Alterations in bioenergetic function induced by Parkinson’s disease mimetic compounds: lack of correlation with superoxide generation. J Neurochem  2012; 122(5): 941-51.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07836.x] [PMID:  22708893] 
[125] 
Zawada WM, Banninger GP, Thornton J, et al. Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. J Neuroinflammation  2011; 8: 129.
[http://dx.doi.org/10.1186/1742-2094-8-129] [PMID:  21975039] 
[126] 
Votyakova TV, Reynolds IJ. Ca2+-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I. J Neurochem  2005; 93(3): 526-37.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03042.x] [PMID:  15836612] 
[127] 
Palacino JJ, Sagi D, Goldberg MS, et al. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem  2004; 279(18): 18614-22.
[http://dx.doi.org/10.1074/jbc.M401135200] [PMID:  14985362] 
[128] 
Gegg ME, Cooper JM, Schapira AH, Taanman JW. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One  2009; 4(3)e4756
[http://dx.doi.org/10.1371/journal.pone.0004756] [PMID:  19270741] 
[129] 
Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci USA  2008; 105(32): 11364-9.
[http://dx.doi.org/10.1073/pnas.0802076105] [PMID:  18687901] 
[130] 
Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA  2010; 107(11): 5018-23.
[http://dx.doi.org/10.1073/pnas.0913485107] [PMID:  20194754] 
[131] 
Jiang H, Ren Y, Zhao J, Feng J. Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis. Hum Mol Genet  2004; 13(16): 1745-54.
[http://dx.doi.org/10.1093/hmg/ddh180] [PMID:  15198987] 
[132] 
Wood-Kaczmar A, Gandhi S, Yao Z, et al. PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS One  2008; 3(6)e2455
[http://dx.doi.org/10.1371/journal.pone.0002455] [PMID:  18560593] 
[133] 
Amo T, Sato S, Saiki S, et al. Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects. Neurobiol Dis  2011; 41(1): 111-8.
[http://dx.doi.org/10.1016/j.nbd.2010.08.027] [PMID:  20817094] 
[134] 
Amo T, Saiki S, Sawayama T, Sato S, Hattori N. Detailed analysis of mitochondrial respiratory chain defects caused by loss of PINK1. Neurosci Lett  2014; 580: 37-40.
[http://dx.doi.org/10.1016/j.neulet.2014.07.045] [PMID:  25092611] 
[135] 
Deas E, Wood NW, Plun-Favreau H. Mitophagy and Parkinson’s disease: the PINK1-parkin link. Biochim Biophys Acta  2011; 1813(4): 623-33.
[http://dx.doi.org/10.1016/j.bbamcr.2010.08.007] [PMID:  20736035] 
[136] 
Vives-Bauza C, Zhou C, Huang Y, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA  2010; 107(1): 378-83.
[http://dx.doi.org/10.1073/pnas.0911187107] [PMID:  19966284] 
[137] 
Narendra DP, Jin SM, Tanaka A, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol  2010; 8(1)e1000298
[http://dx.doi.org/10.1371/journal.pbio.1000298] [PMID:  20126261] 
[138] 
de Vries RLA, Przedborski S. Mitophagy and Parkinson’s disease: be eaten to stay healthy. Mol Cell Neurosci  2013; 55: 37-43.
[http://dx.doi.org/10.1016/j.mcn.2012.07.008] [PMID:  22926193] 
[139] 
Michel PP, Hirsch EC, Hunot S. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron  2016; 90(4): 675-91.
[http://dx.doi.org/10.1016/j.neuron.2016.03.038] [PMID:  27196972] 
[140] 
Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules  2010; 15(11): 7792-814.
[http://dx.doi.org/10.3390/molecules15117792] [PMID:  21060289] 
[141] 
Ebrahimi A, Schluesener H. Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing Res Rev  2012; 11(2): 329-45.
[http://dx.doi.org/10.1016/j.arr.2012.01.006] [PMID:  22336470] 
[142] 
Pérez-Jiménez J, Neveu V, Vos F, Scalbert A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr  2010; 64(Suppl. 3): S112-20.
[http://dx.doi.org/10.1038/ejcn.2010.221] [PMID:  21045839] 
[143] 
Shahpiri Z, Bahramsoltani R, Hosein Farzaei M, Farzaei F, Rahimi R. Phytochemicals as future drugs for Parkinson’s disease: a comprehensive review. Rev Neurosci  2016; 27(6): 651-68.
[http://dx.doi.org/10.1515/revneuro-2016-0004] [PMID:  27124673] 
[144] 
Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging  2002; 23(5): 719-35.
[http://dx.doi.org/10.1016/S0197-4580(02)00078-7] [PMID:  12392777] 
[145] 
DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets  2000; 1(1): 25-58.
[http://dx.doi.org/10.2174/1389450003349380] [PMID:  11475535] 
[146] 
Pardon MC, Joubert C, Perez-Diaz F, Christen Y, Launay JM, Cohen-Salmon C. In vivo regulation of cerebral monoamine oxidase activity in senescent controls and chronically stressed mice by long-term treatment with Ginkgo biloba extract (EGb 761). Mech Ageing Dev  2000; 113(3): 157-68.
[http://dx.doi.org/10.1016/S0047-6374(99)00107-4] [PMID:  10714935] 
[147] 
Rojas P, Rojas C, Ebadi M, Montes S, Monroy-Noyola A, Serrano-García N. EGb761 pretreatment reduces monoamine oxidase activity in mouse corpus striatum during 1-methyl-4-phenylpyridinium neurotoxicity. Neurochem Res  2004; 29(7): 1417-23.
[http://dx.doi.org/10.1023/B:NERE.0000026406.64547.93] [PMID:  15202774] 
[148] 
Rojas P, Garduño B, Rojas C, et al. EGb761 blocks MPP+-induced lipid peroxidation in mouse corpus striatum. Neurochem Res  2001; 26(11): 1245-51.
[http://dx.doi.org/10.1023/A:1013971524150] [PMID:  11874207] 
[149] 
Rojas P, Ruiz-Sánchez E, Rojas C, Ogren SO. Ginkgo biloba extract (EGb 761) modulates the expression of dopamine-related genes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. Neuroscience  2012; 223: 246-57.
[http://dx.doi.org/10.1016/j.neuroscience.2012.08.004] [PMID:  22885234] 
[150] 
Rojas P, Serrano-García N, Mares-Sámano JJ, Medina-Campos ON, Pedraza-Chaverri J, Ogren SO. EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice: role of oxidative stress. Eur J Neurosci  2008; 28(1): 41-50.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06314.x] [PMID:  18662333] 
[151] 
Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD. Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol  2002; 155(8): 732-8.
[http://dx.doi.org/10.1093/aje/155.8.732] [PMID:  11943691] 
[152] 
Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. Coffee and tea consumption and the risk of Parkinson’s disease. Mov Disord  2007; 22(15): 2242-8.
[http://dx.doi.org/10.1002/mds.21706] [PMID:  17712848] 
[153] 
Li FJ, Ji HF, Shen L. A meta-analysis of tea drinking and risk of Parkinson’s disease. Scientific World Journal 2012.2012923464
[http://dx.doi.org/10.1100/2012/923464] [PMID:  22448141] 
[154] 
Qi H, Li S. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr Gerontol Int  2014; 14(2): 430-9.
[http://dx.doi.org/10.1111/ggi.12123] [PMID:  23879665] 
[155] 
Mandel SA, Amit T, Kalfon L, Reznichenko L, Youdim MB. Targeting multiple neurodegenerative diseases etiologies with multimodal-acting green tea catechins. J Nutr  2008; 138(8): 1578S-83S.
[http://dx.doi.org/10.1093/jn/138.8.1578S] [PMID:  18641210] 
[156] 
Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S. Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem  2001; 78(5): 1073-82.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00490.x] [PMID:  11553681] 
[157] 
Choi JY, Park CS, Kim DJ, et al. Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease in mice by tea phenolic epigallocatechin 3-gallate. Neurotoxicology  2002; 23(3): 367-74.
[http://dx.doi.org/10.1016/S0161-813X(02)00079-7] [PMID:  12387363] 
[158] 
Kim JS, Kim JM. O JJ, Jeon BS. Inhibition of inducible nitric oxide synthase expression and cell death by (-)-epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. J Clin Neurosci  2010; 17(9): 1165-8.
[http://dx.doi.org/10.1016/j.jocn.2010.01.042] [PMID:  20541420] 
[159] 
Xu Q, Langley M, Kanthasamy AG, Reddy MB. Epigallocatechin gallate has a neurorescue effect in a mouse model of parkinson disease. J Nutr  2017; 147(10): 1926-31.
[http://dx.doi.org/10.3945/jn.117.255034] [PMID:  28835392] 
[160] 
Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules  2010; 15(10): 7313-52.
[http://dx.doi.org/10.3390/molecules15107313] [PMID:  20966876] 
[161] 
de Souza RF, De Giovani WF. Antioxidant properties of complexes of flavonoids with metal ions. Redox Rep  2004; 9(2): 97-104.
[http://dx.doi.org/10.1179/135100004225003897] [PMID:  15231064] 
[162] 
van Acker SA, van den Berg DJ, Tromp MN, et al. Structural aspects of antioxidant activity of flavonoids. Free Radic Biol Med  1996; 20(3): 331-42.
[http://dx.doi.org/10.1016/0891-5849(95)02047-0] [PMID:  8720903] 
[163] 
Grinberg LN, Newmark H, Kitrossky N, Rahamim E, Chevion M, Rachmilewitz EA. Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol  1997; 54(9): 973-8.
[http://dx.doi.org/10.1016/S0006-2952(97)00155-X] [PMID:  9374417] 
[164] 
Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem  2010; 345(1-2): 91-104.
[http://dx.doi.org/10.1007/s11010-010-0563-x] [PMID:  20730621] 
[165] 
Mandel S, Maor G, Youdim MB. Iron and alpha-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol (-)-epigallocatechin-3-gallate. J Mol Neurosci  2004; 24(3): 401-16.
[http://dx.doi.org/10.1385/JMN:24:3:401] [PMID:  15655262] 
[166] 
Perron NR, Hodges JN, Jenkins M, Brumaghim JL. Predicting how polyphenol antioxidants prevent DNA damage by binding to iron. Inorg Chem  2008; 47(14): 6153-61.
[http://dx.doi.org/10.1021/ic7022727] [PMID:  18553907] 
[167] 
Mounsey RB, Teismann P. Chelators in the treatment of iron accumulation in Parkinson’s disease. Int J Cell Biol 2012.2012983245
[http://dx.doi.org/10.1155/2012/983245] [PMID:  22754573] 
[168] 
Daniel S, Limson JL, Dairam A, Watkins GM, Daya S. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem  2004; 98(2): 266-75.
[http://dx.doi.org/10.1016/j.jinorgbio.2003.10.014] [PMID:  14729307] 
[169] 
Du XX, Xu HM, Jiang H, Song N, Wang J, Xie JX. Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurosci Bull  2012; 28(3): 253-8.
[http://dx.doi.org/10.1007/s12264-012-1238-2] [PMID:  22622825] 
[170] 
Dai MC, Zhong ZH, Sun YH, et al. Curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis. Neurosci Lett  2013; 536: 41-6.
[http://dx.doi.org/10.1016/j.neulet.2013.01.007] [PMID:  23328441] 
[171] 
Gupta SC, Prasad S, Kim JH, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep  2011; 28(12): 1937-55.
[http://dx.doi.org/10.1039/c1np00051a] [PMID:  21979811] 
[172] 
Khatri DK, Juvekar AR. Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson’s disease. Pharmacol Biochem Behav  2016; 150-151: 39-47.
[http://dx.doi.org/10.1016/j.pbb.2016.09.002] [PMID:  27619637] 
[173] 
Harish G, Venkateshappa C, Mythri RB, et al. Bioconjugates of curcumin display improved protection against glutathione depletion mediated oxidative stress in a dopaminergic neuronal cell line: Implications for Parkinson’s disease. Bioorg Med Chem  2010; 18(7): 2631-8.
[http://dx.doi.org/10.1016/j.bmc.2010.02.029] [PMID:  20227282] 
[174] 
Dickinson DA, Iles KE, Zhang H, Blank V, Forman HJ. Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression. FASEB J  2003; 17(3): 473-5.
[http://dx.doi.org/10.1096/fj.02-0566fje] [PMID:  12514113] 
[175] 
Jagatha B, Mythri RB, Vali S, Bharath MM. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson’s disease explained via in silico studies. Free Radic Biol Med  2008; 44(5): 907-17.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.11.011] [PMID:  18166164] 
[176] 
Pandareesh MD, Shrivash MK, Naveen Kumar HN, Misra K, Srinivas Bharath MM. Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson’s Disease. Neurochem Res  2016; 41(11): 3113-28.
[http://dx.doi.org/10.1007/s11064-016-2034-6] [PMID:  27535828] 
[177] 
Rojas C, Rojas-Castaneda J, Ruiz-Sanchez E, Montes P, Rojas P. Antioxidant properties of a Ginkgo biloba leaf extract (EGb 761) in animal models of Alzheimer’s and Parkinson’s diseases. Curr Top Nutraceutical Res  2015; 13: 105.
[178] 
Tanaka K, Galduróz RF, Gobbi LT, Galduróz JC. Ginkgo biloba extract in an animal model of Parkinson’s disease: a systematic review. Curr Neuropharmacol  2013; 11(4): 430-5.
[http://dx.doi.org/10.2174/1570159X11311040006] [PMID:  24381532] 
[179] 
Ahmad M, Saleem S, Ahmad AS, et al. Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. J Neurochem  2005; 93(1): 94-104.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03000.x] [PMID:  15773909] 
[180] 
Tellone E, Galtieri A, Russo A, Giardina B, Ficarra S. Resveratrol: A focus on several neurodegenerative diseases. Oxid Med Cell Longev 2015.2015392169
[http://dx.doi.org/10.1155/2015/392169] [PMID:  26180587] 
[181] 
Fukui M, Choi HJ, Zhu BT. Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death. Free Radic Biol Med  2010; 49(5): 800-13.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.06.002] [PMID:  20542495] 
[182] 
Moldzio R, Radad K, Krewenka C, Kranner B, Duvigneau JC, Rausch WD. Protective effects of resveratrol on glutamate-induced damages in murine brain cultures. J Neural Transm (Vienna)  2013; 120(9): 1271-80.
[http://dx.doi.org/10.1007/s00702-013-1000-6] [PMID:  23459926] 
[183] 
Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell  2006; 127(6): 1109-22.
[http://dx.doi.org/10.1016/j.cell.2006.11.013] [PMID:  17112576] 
[184] 
Wu Y, Li X, Zhu JX, et al. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals  2011; 19(3): 163-74.
[http://dx.doi.org/10.1159/000328516] [PMID:  21778691] 
[185] 
Lin T-K, Chen S-D, Chuang Y-C, et al. Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy. Int J Mol Sci  2014; 15(1): 1625-46.
[http://dx.doi.org/10.3390/ijms15011625] [PMID:  24451142] 
[186] 
Ferretta A, Gaballo A, Tanzarella P, et al. Effect of resveratrol on mitochondrial function: implications in parkin-associated familiar Parkinson’s disease. Biochim Biophys Acta  2014; 1842(7): 902-15.
[http://dx.doi.org/10.1016/j.bbadis.2014.02.010] [PMID:  24582596] 
[187] 
Mathieu L, Lopes Costa A, Le Bachelier C, et al. Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3. Free Radic Biol Med  2016; 96: 190-8.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.027] [PMID:  27126960] 
[188] 
Peng K, Tao Y, Zhang J, et al. Resveratrol regulates mitochondrial
biogenesis and fission/fusion to attenuate rotenone-induced neurotoxicity.
2015; 2015 
[189] 
Boots AW, Haenen GRMM, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol  2008; 585(2-3): 325-37.
[http://dx.doi.org/10.1016/j.ejphar.2008.03.008] [PMID:  18417116] 
[190] 
Karuppagounder SS, Madathil SK, Pandey M, Haobam R, Rajamma U, Mohanakumar KP. Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience  2013; 236: 136-48.
[http://dx.doi.org/10.1016/j.neuroscience.2013.01.032] [PMID:  23357119] 
[191] 
Sharma DR, Wani WY, Sunkaria A, et al. Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus. Neuroscience  2016; 324: 163-76.
[http://dx.doi.org/10.1016/j.neuroscience.2016.02.055] [PMID:  26944603] 
[192] 
Ay M, Luo J, Langley M, et al. Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson’s Disease. J Neurochem  2017; 141(5): 766-82.
[http://dx.doi.org/10.1111/jnc.14033] [PMID:  28376279] 
[193] 
Singh N, Haldar S, Tripathi AK, et al. Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal  2014; 20(8): 1324-63.
[http://dx.doi.org/10.1089/ars.2012.4931] [PMID:  23815406] 
[194] 
Kandinov B, Giladi N, Korczyn AD. Smoking and tea consumption delay onset of Parkinson’s disease. Parkinsonism Relat Disord  2009; 15(1): 41-6.
[http://dx.doi.org/10.1016/j.parkreldis.2008.02.011] [PMID:  18434232] 
[195] 
Pasinetti GM, Wang J, Ho L, Zhao W, Dubner L. Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochim Biophys Acta  2015; 1852(6): 1202-8.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.006] [PMID:  25315300] 
[196] 
Colizzi C. The protective effects of polyphenols on Alzheimer’s disease: A systematic review. Alzheimers Dement (N Y)  2018; 5: 184-96.
[http://dx.doi.org/10.1016/j.trci.2018.09.002] [PMID:  31194101] 
[197] 
Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol  2008; 28(1): 110-3.
[http://dx.doi.org/10.1097/jcp.0b013e318160862c] [PMID:  18204357] 
[198] 
Turner RS, Thomas RG, Craft S, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology  2015; 85(16): 1383-91.
[http://dx.doi.org/10.1212/WNL.0000000000002035] [PMID:  26362286] 
[199] 
Moussa C, Hebron M, Huang X, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation  2017; 14(1): 1.
[http://dx.doi.org/10.1186/s12974-016-0779-0] [PMID:  28086917] 
[200] 
Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res  2012; 46(6): 716-23.
[http://dx.doi.org/10.1016/j.jpsychires.2012.03.003] [PMID:  22459264] 
[201] 
Ihl R. Effects of Ginkgo biloba extract EGb 761 ® in dementia with neuropsychiatric features: review of recently completed randomised, controlled trials. Int J Psychiatry Clin Pract  2013; 17(Suppl. 1): 8-14.
[http://dx.doi.org/10.3109/13651501.2013.814796] [PMID:  23808613] 
[202] 
Maclennan KM, Darlington CL, Smith PF. The CNS effects of Ginkgo biloba extracts and ginkgolide B. Prog Neurobiol  2002; 67(3): 235-57.
[http://dx.doi.org/10.1016/S0301-0082(02)00015-1] [PMID:  12169298] 
[203] 
Napryeyenko O, Sonnik G, Tartakovsky I. Efficacy and tolerability of Ginkgo biloba extract EGb 761 by type of dementia: analyses of a randomised controlled trial. J Neurol Sci  2009; 283(1-2): 224-9.
[http://dx.doi.org/10.1016/j.jns.2009.02.353] [PMID:  19286192] 
[204] 
Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther  2012; 4(5): 43.
[http://dx.doi.org/10.1186/alzrt146] [PMID:  23107780] 
[205] 
Gauthier S, Schlaefke S. Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Interv Aging  2014; 9: 2065-77.
[http://dx.doi.org/10.2147/CIA.S72728] [PMID:  25506211] 
[206] 
Savaskan E, Mueller H, Hoerr R, von Gunten A, Gauthier S.
Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum
of behavioral and psychological symptoms of dementia: metaanalysis
of randomized controlled trials. 2018; 285-93. 
[207] 
Pagano E, Romano B, Izzo AA, Borrelli F. The clinical efficacy of curcumin-containing nutraceuticals: An overview of systematic reviews. Pharmacol Res  2018; 134: 79-91.
[http://dx.doi.org/10.1016/j.phrs.2018.06.007] [PMID:  29890252] 
[208] 
Lewandowska U, Szewczyk K, Hrabec E, Janecka A, Gorlach S. Overview of metabolism and bioavailability enhancement of polyphenols. J Agric Food Chem  2013; 61(50): 12183-99.
[http://dx.doi.org/10.1021/jf404439b] [PMID:  24295170] 
[209] 
Molino S, Dossena M, Buonocore D, et al. Polyphenols in dementia: From molecular basis to clinical trials. Life Sci  2016; 161: 69-77.
[http://dx.doi.org/10.1016/j.lfs.2016.07.021] [PMID:  27493077] 
[210] 
Barnes S, Prasain J, D’Alessandro T, et al. The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct  2011; 2(5): 235-44.
[http://dx.doi.org/10.1039/c1fo10025d] [PMID:  21779561] 
[211] 
Figueira I, Menezes R, Macedo D, Costa I, Dos Santos CN. Polyphenols Beyond Barriers: A Glimpse into the Brain. Curr Neuropharmacol  2017; 15(4): 562-94.
[http://dx.doi.org/10.2174/1570159X14666161026151545] [PMID:  27784225] 
[212] 
Youdim KA, Shukitt-Hale B, Joseph JA. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med  2004; 37(11): 1683-93.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.08.002] [PMID:  15528027] 
[213] 
Renaud J, Martinoli MG. Considerations for the Use of Polyphenols as Therapies in neurodegenerative diseases. Int J Mol Sci  2019; 20(8): 1883.
[http://dx.doi.org/10.3390/ijms20081883] [PMID:  30995776] 
[214] 
Kujawska M, Jodynis-Liebert J. Polyphenols in parkinson’s disease: A systematic review of in vivo studies. Nutrients  2018; 10(5): 642.
[http://dx.doi.org/10.3390/nu10050642] [PMID:  29783725] 
[215] 
Modi G, Pillay V, Choonara YE. Advances in the treatment of neurodegenerative disorders employing nanotechnology. Ann N Y Acad Sci  2010; 1184: 154-72.
[http://dx.doi.org/10.1111/j.1749-6632.2009.05108.x] [PMID:  20146696] 
[216] 
Sandhir R, Yadav A, Sunkaria A, Singhal N. Nano-antioxidants: An emerging strategy for intervention against neurodegenerative conditions. Neurochem Int  2015; 89: 209-26.
[http://dx.doi.org/10.1016/j.neuint.2015.08.011] [PMID:  26315960] 
[217] 
Wang Y, Xu H, Fu Q, Ma R, Xiang J. Protective effect of resveratrol derived from Polygonum cuspidatum and its liposomal form on nigral cells in parkinsonian rats. J Neurol Sci  2011; 304(1-2): 29-34.
[http://dx.doi.org/10.1016/j.jns.2011.02.025] [PMID:  21376343] 
[218] 
da Rocha Lindner G, Bonfanti Santos D, Colle D, et al. Improved neuroprotective effects of resveratrol-loaded polysorbate 80-coated poly(lactide) nanoparticles in MPTP-induced Parkinsonism. Nanomedicine (Lond)  2015; 10(7): 1127-38.
[http://dx.doi.org/10.2217/nnm.14.165] [PMID:  25929569] 
[219] 
Palle S, Neerati P. Improved neuroprotective effect of resveratrol nanoparticles as evinced by abrogation of rotenone-induced behavioral deficits and oxidative and mitochondrial dysfunctions in rat model of Parkinson’s disease. Naunyn Schmiedebergs Arch Pharmacol  2018; 391(4): 445-53.
[http://dx.doi.org/10.1007/s00210-018-1474-8] [PMID:  29411055] 
[220] 
Pandita D, Kumar S, Poonia N, Lather V. Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol. Food Res Int  2014; 62: 1165-74.
[http://dx.doi.org/10.1016/j.foodres.2014.05.059] 
[221] 
Yadav A, Sunkaria A, Singhal N, Sandhir R. Resveratrol loaded solid lipid nanoparticles attenuate mitochondrial oxidative stress in vascular dementia by activating Nrf2/HO-1 pathway. Neurochem Int  2018; 112: 239-54.
[http://dx.doi.org/10.1016/j.neuint.2017.08.001] [PMID:  28782592] 
[222] 
Bollimpelli VS, Kumar P, Kumari S, Kondapi AK. Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity. Neurochem Int  2016; 95: 37-45.
[http://dx.doi.org/10.1016/j.neuint.2016.01.006] [PMID:  26826319] 
[223] 
Kanai M, Imaizumi A, Otsuka Y, et al. Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol  2012; 69(1): 65-70.
[http://dx.doi.org/10.1007/s00280-011-1673-1] [PMID:  21603867] 
[224] 
Dos Santos MCT, Scheller D, Schulte C, et al. Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis. PLoS One  2018; 13(11)e0206536
[http://dx.doi.org/10.1371/journal.pone.0206536] [PMID:  30383831] 
[225] 
Miller DB, O’Callaghan JP. Biomarkers of Parkinson’s disease: present and future. Metabolism  2015; 64(3)(Suppl. 1): S40-6.
[http://dx.doi.org/10.1016/j.metabol.2014.10.030] [PMID:  25510818] 
[226] 
Hall S, Surova Y, Öhrfelt A, Zetterberg H, Lindqvist D, Hansson O. CSF biomarkers and clinical progression of Parkinson disease. Neurology  2015; 84(1): 57-63.
[http://dx.doi.org/10.1212/WNL.0000000000001098] [PMID:  25411441] 
[227] 
Mollenhauer B, Caspell-Garcia CJ, Coffey CS, et al. Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology  2017; 89(19): 1959-69.
[http://dx.doi.org/10.1212/WNL.0000000000004609] [PMID:  29030452] 
[228] 
Sharma S, Moon CS, Khogali A, et al. Biomarkers in Parkinson’s disease (recent update). Neurochem Int  2013; 63(3): 201-29.
[http://dx.doi.org/10.1016/j.neuint.2013.06.005] [PMID:  23791710] 
[229] 
Ide K, Yamada H, Umegaki K, et al. Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson’s disease. Nutrition  2015; 31(2): 406-8.
[http://dx.doi.org/10.1016/j.nut.2014.08.001] [PMID:  25592020] 
[230] 
He R, Yan X, Guo J, Xu Q, Tang B, Sun Q. Recent advances in biomarkers for parkinson’s disease. Front Aging Neurosci  2018; 10: 305.
[http://dx.doi.org/10.3389/fnagi.2018.00305] [PMID:  30364199] 
[231] 
Lotankar S, Prabhavalkar KS, Bhatt LK. Biomarkers for parkinson’s disease: recent advancement. Neurosci Bull  2017; 33(5): 585-97.
[http://dx.doi.org/10.1007/s12264-017-0183-5] [PMID:  28936761] 
[232] 
Lin X, Cook TJ, Zabetian CP, et al. DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep  2012; 2: 954.
[http://dx.doi.org/10.1038/srep00954] [PMID:  23233873] 
[233] 
Saito Y. Oxidized DJ-1 as a possible biomarker of Parkinson’s disease. J Clin Biochem Nutr  2014; 54(3): 138-44.
[http://dx.doi.org/10.3164/jcbn.13-108] [PMID:  24894116] 
[234] 
Shen L, Ji H-F. Low uric acid levels in patients with Parkinson’s disease: evidence from meta-analysis. BMJ Open  2013; 3(11)e003620
[http://dx.doi.org/10.1136/bmjopen-2013-003620] [PMID:  24247326] 
[235] 
Wen M, Zhou B, Chen YH, et al. Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis. PLoS One  2017; 12(3)e0173731
[http://dx.doi.org/10.1371/journal.pone.0173731] [PMID:  28319195] 
[236] 
Boots AW, Haenen GRMM, Bast A. Health effects of quercetin:
From antioxidant to nutraceutical. 2008; 325-7. 
[237] 
Murakami A. Dose-dependent functionality and toxicity of green tea polyphenols in experimental rodents. Arch Biochem Biophys  2014; 557: 3-10.
[http://dx.doi.org/10.1016/j.abb.2014.04.018] [PMID:  24814373] 
[238] 
Hu J, Webster D, Cao J, Shao A. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regul Toxicol Pharmacol  2018; 95: 412-33.
[http://dx.doi.org/10.1016/j.yrtph.2018.03.019] [PMID:  29580974] 
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DOI https://dx.doi.org/10.2174/1389450120666191017120505	Print ISSN 1389-4501
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