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

Current Drug Targets - Tập 21 Số 5 - Trang 458-476 - 2020
Suet Lee Hor1, Seong Lin Teoh2, Wei Ling Lim1
1Department of Biological Sciences, School of Science and Technology, Sunway University, 47500 Selangor, Malaysia
2Department of Anatomy, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia

Tóm tắt

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.

Từ khóa


Tài liệu tham khảo

Dexter D.T.; Jenner P.; Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 2013,62,132-144

Pringsheim T.; Jette N.; Frolkis A.; Steeves T.D.; The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2014,29(13),1583-1590

Obeso J.A.; Rodriguez-Oroz M.C.; Goetz C.G.; Missing pieces in the Parkinson’s disease puzzle. Nat Med 2010,16(6),653-661

Baradaran N.; Tan S.N.; Liu A.; Parkinson’s disease rigidity: relation to brain connectivity and motor performance. Front Neurol 2013,4,67

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

Chaudhuri K.R.; Schapira A.H.V.; Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009,8(5),464-474

Kalia L.V.; Lang A.E.; Parkinson’s disease. Lancet 2015,386(9996),896-912

Plowman E.K.; Kleim J.A.; Behavioral and neurophysiological correlates of striatal dopamine depletion: a rodent model of Parkinson’s disease. J Commun Disord 2011,44(5),549-556

Dickson D.W.; Braak H.; Duda J.E.; Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol 2009,8(12),1150-1157

Gerfen C.R.; Surmeier D.J.; Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 2011,34,441-466

Luk K.C.; Kehm V.; Carroll J.; Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012,338(6109),949-953

Del Tredici K.; Duda J.E.; Peripheral Lewy body pathology in Parkinson’s disease and incidental Lewy body disease: four cases. J Neurol Sci 2011,310(1-2),100-106

Tong J.; Wong H.; Guttman M.; Brain alpha-synuclein accumulation in multiple system atrophy, Parkinson’s disease and progressive supranuclear palsy: a comparative investigation. Brain 2010,133(Pt 1),172-188

Moore D.J.; West A.B.; Dawson V.L.; Dawson T.M.; Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 2005,28,57-87

Büeler H.; Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson’s disease. Exp Neurol 2009,218(2),235-246

Thomas B.; Beal M.F.; Molecular insights into Parkinson’s disease. F1000 Med Rep 2011,3,7

Gorell J.M.; Johnson C.C.; Rybicki B.A.; Peterson E.L.; Richardson R.J.; The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998,50(5),1346-1350

Schapira A.H.; Jenner P.; Etiology and pathogenesis of Parkinson’s disease. Mov Disord 2011,26(6),1049-1055

Noyce A.J.; Bestwick J.P.; Silveira-Moriyama L.; Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol 2012,72(6),893-901

Langston J.W.; Ballard P.; Tetrud J.W.; Irwin I.; Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983,219(4587),979-980

Tanner C.M.; Kamel F.; Ross G.W.; Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 2011,119(6),866-872

Silva B.A.; Breydo L.; Fink A.L.; Uversky V.N.; Agrochemicals, α-synuclein, and Parkinson’s disease. Mol Neurobiol 2013,47(2),598-612

Betarbet R.; Sherer T.B.; MacKenzie G.; Garcia-Osuna M.; Panov A.V.; Greenamyre J.T.; Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000,3(12),1301-1306

Cannon J.R.; Tapias V.; Na H.M.; Honick A.S.; Drolet R.E.; Greenamyre J.T.; A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 2009,34(2),279-290

Xicoy H.; Wieringa B.; Martens G.J.M.; The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Mol Neurodegener 2017,12(1),10

Jalewa J.; Sharma M.K.; 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

Katzenschlager R.; Lees A.J.; Treatment of Parkinson’s disease: levodopa as the first choice. J Neurol 2002,249(Suppl. 2),II19-II24

Hornykiewicz O.; A brief history of levodopa. J Neurol 2010,257(Suppl. 2),S249-S252

Mallajosyula J.K.; Kaur D.; Chinta S.J.; MAO-B elevation in mouse brain astrocytes results in Parkinson’s pathology. PLoS One 2008,3(2)

Simola N.; Emerging drugs and targets for Parkinson’s disease 2014,61-82

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),1735-1749

Cools R.; Barker R.A.; Sahakian B.J.; Robbins T.W.; L-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease. Neuropsychologia 2003,41(11),1431-1441

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),533-534

Li B.D.; Bi Z.Y.; Liu J.F.; Adverse effects produced by different drugs used in the treatment of Parkinson’s disease: A mixed treatment comparison. CNS Neurosci Ther 2017,23(10),827-842

Rascol O.; Brooks D.J.; Korczyn A.D.; De Deyn P.P.; Clarke C.E.; Lang A.E.; 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),1484-1491

Fedorova T.; Logvinenko A.; Poleshchuk V.; Illarioshkin S.; The state of systemic oxidative stress during Parkinson’s disease. Neurochem J 2017,11,340-345

Hwang O.; Role of oxidative stress in Parkinson’s disease. Exp Neurobiol 2013,22(1),11-17

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

Uttara B.; Singh A.V.; Zamboni P.; Mahajan R.T.; Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009,7(1),65-74

Almeida S.; Alves M.G.; Sousa M.; Oliveira P.F.; Silva B.M.; Are polyphenols strong dietary agents against neurotoxicity and neurodegeneration? Neurotox Res 2016,30(3),345-366

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

Pandey K.B.; Rizvi S.I.; Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009,2(5),270-278

Melo A.; Monteiro L.; Lima R.M.; Oliveira D.M.; Cerqueira M.D.; El-Bachá R.S.; Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives. Oxid Med Cell Longev 2011

Jellinger K.A.; Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med 2010,14(3),457-487

Valencia A.; Morán J.; Reactive oxygen species induce different cell death mechanisms in cultured neurons. Free Radic Biol Med 2004,36(9),1112-1125

Dias V.; Junn E.; Mouradian M.M.; The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 2013,3(4),461-491

Kobayashi H.; Fukuhara K.; Tada-Oikawa S.; 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

Goodwin J.; Nath S.; Engelborghs Y.; Pountney D.L.; Raised calcium and oxidative stress cooperatively promote alpha-synuclein aggregate formation. Neurochem Int 2013,62(5),703-711

Sanders L.H.; Timothy Greenamyre J.; Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol Med 2013,62,111-120

Garbarino V.R.; Orr M.E.; Rodriguez K.A.; Buffenstein R.; Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates. Arch Biochem Biophys 2015,576,8-16

Duan W.; Zhu X.; Ladenheim B.; p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism. Ann Neurol 2002,52(5),597-606

Herbin M.; Simonis C.; Revéret L.; Dopamine modulates motor control in a specific plane related to support. PLoS One 2016,11(5)

Ershov P.V.; Ugrumov M.V.; Calas A.; Makarenko I.G.; 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

Nirenberg M.J.; Chan J.; Liu Y.; Edwards R.H.; Pickel V.M.; 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),4135-4145

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),165-176

Vergo S.; Johansen J.L.; 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

Chen L.; Ding Y.; Cagniard B.; Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci 2008,28(2),425-433

Caudle W.M.; Richardson J.R.; Wang M.Z.; Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci 2007,27(30),8138-8148

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),154-157

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

Uhl G.R.; Li S.; Takahashi N.; The VMAT2 gene in mice and humans: amphetamine responses, locomotion, cardiac arrhythmias, aging, and vulnerability to dopaminergic toxins. FASEB J 2000,14(15),2459-2465

Pifl C.; Rajput A.; Reither H.; 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),8210-8218

Basma A.N.; Morris E.J.; Nicklas W.J.; Geller H.M.; L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation. J Neurochem 1995,64(2),825-832

Jinsmaa Y.; Florang V.R.; Rees J.N.; Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson’s disease. Chem Biol Interact 2011,192(1-2),118-121

Doorn J.A.; Florang V.R.; Schamp J.H.; Vanle B.C.; Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons. Parkinsonism Relat Disord 2014,20(Suppl. 1),S73-S75

Cohen G.; Oxidative stress, mitochondrial respiration, and Parkinson’s disease. Ann N Y Acad Sci 2000,899,112-120

Anderson D.G.; Mariappan S.V.; Buettner G.R.; Doorn J.A.; Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone. J Biol Chem 2011,286(30),26978-26986

Rabinovic A.D.; Lewis D.A.; Hastings T.G.; Role of oxidative changes in the degeneration of dopamine terminals after injection of neurotoxic levels of dopamine. Neuroscience 2000,101(1),67-76

Müller T.; Muhlack S.; Cysteinyl-glycine reduction as marker for levodopa-induced oxidative stress in Parkinson’s disease patients. Mov Disord 2011,26(3),543-546

Post M.R.; Lieberman O.J.; Mosharov E.V.; Can interactions between α-synuclein, dopamine and calcium explain selective neurodegeneration in Parkinson’s Disease? Front Neurosci 2018,12,161

Sulzer D.; Zecca L.; Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 2000,1(3),181-195

Fleming R.E.; Ponka P.; Iron overload in human disease. N Engl J Med 2012,366(4),348-359

Beard J.; Iron deficiency alters brain development and functioning. J Nutr 2003,133(5)(Suppl. 1),1468S-1472S

Unger E.L.; Wiesinger J.A.; Hao L.; Beard J.L.; Dopamine D2 receptor expression is altered by changes in cellular iron levels in PC12 cells and rat brain tissue. J Nutr 2008,138(12),2487-2494

Wilkinson N.; Pantopoulos K.; The IRP/IRE system in vivo: insights from mouse models. Front Pharmacol 2014,5,176

Mills E.; Dong X.P.; Wang F.; Xu H.; Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders. Future Med Chem 2010,2(1),51-64

Haacke E.M.; Cheng N.Y.C.; House M.J.; Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging 2005,23(1),1-25

Sian-Hülsmann J.; Mandel S.; Youdim M.B.; Riederer P.; The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem 2011,118(6),939-957

Dexter D.T.; Carayon A.; Javoy-Agid F.; 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),1953-1975

Morawski M.; Meinecke C.; Reinert T.; Determination of trace elements in the human substantia nigra. Nucl Instrum Methods Phys Res B 2005,231,224-228

Kaur D.; Yantiri F.; Rajagopalan S.; Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson’s disease. Neuron 2003,37(6),899-909

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

Ayton S.; Lei P.; Adlard P.A.; Iron accumulation confers neurotoxicity to a vulnerable population of nigral neurons: implications for Parkinson’s disease. Mol Neurodegener 2014,9,27

Weinreb O.; Mandel S.; Youdim M.B.H.; Amit T.; Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Free Radic Biol Med 2013,62,52-64

Lee D.W.; Andersen J.K.; Iron elevations in the aging Parkinsonian brain: a consequence of impaired iron homeostasis? J Neurochem 2010,112(2),332-339

Carroll C.B.; Zeissler M.L.; Chadborn N.; Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson’s disease. Neurochem Int 2011,59(1),73-80

Kalivendi S.V.; Kotamraju S.; Cunningham S.; Shang T.; Hillard C.J.; 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),151-164

Bokare A.D.; Choi W.; Review of iron-free Fenton-like systems for activating H2O2 in advanced oxidation processes. J Hazard Mater 2014,275,121-135

LaVaute T.; Smith S.; Cooperman S.; 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),209-214

Salvatore M.F.; Fisher B.; Surgener S.P.; Gerhardt G.A.; 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),341-347

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),576-580

Zhou Z.D.; Tan E.K.; Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases. Mol Neurodegener 2017,12(1),75

Ayala A.; Muñoz M.F.; Argüelles S.; Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014

Sánchez Campos S.; Rodríguez Diez G.; Oresti G.M.; Salvador G.A.; Dopaminergic neurons respond to iron-induced oxidative stress by modulating lipid acylation and deacylation cycles. PLoS One 2015,10(6)

Bertrand R.L.; Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events. Med Hypotheses 2017,101,69-74

Shamoto-Nagai M.; Maruyama W.; Akao Y.; Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells. J Neural Transm (Vienna) 2004,111(10-11),1253-1265

Shamoto-Nagai M.; Maruyama W.; Hashizume Y.; 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),1559-1567

Uversky V.N.; Li J.; Fink A.L.; 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),44284-44296

Marengo B.; Nitti M.; Furfaro A.L.; Redox homeostasis and cellular antioxidant systems: crucial players in cancer growth and therapy. Oxid Med Cell Longev 2016

Kim G.H.; Kim J.E.; Rhie S.J.; Yoon S.; The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 2015,24(4),325-340

He L.; He T.; Farrar S.; Ji L.; Liu T.; Ma X.; Antioxidants. Cell Physiol Biochem 2017,44(2),532-553

Aoyama K.; Watabe M.; Nakaki T.; Regulation of neuronal glutathione synthesis. J Pharmacol Sci 2008,108(3),227-238

Smeyne M.; Smeyne R.J.; Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med 2013,62,13-25

Commandeur J.N.; Stijntjes G.J.; Vermeulen N.P.; 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

Sian J.; Dexter D.T.; Lees A.J.; Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 1994,36(3),348-355

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.

Chinta S.J.; Kumar M.J.; Hsu M.; Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration. J Neurosci 2007,27(51),13997-14006

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),475-485

Mythri R.B.; Venkateshappa C.; Harish G.; 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),1452-1463

Venkateshappa C.; Harish G.; Mythri R.B.; Mahadevan A.; Bharath M.M.; Shankar S.K.; 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),358-369

Ramsey C.P.; Glass C.A.; Montgomery M.B.; Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol 2007,66(1),75-85

Hybertson B.M.; Gao B.; Bose S.K.; McCord J.M.; Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med 2011,32(4-6),234-246

de Vries H.E.; Witte M.; Hondius D.; Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med 2008,45(10),1375-1383

Lastres-Becker I.; Ulusoy A.; Innamorato N.G.; 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),3173-3192

Turrens J.F.; Mitochondrial formation of reactive oxygen species. J Physiol 2003,552(Pt 2),335-344

Murphy M.P.; How mitochondria produce reactive oxygen species. Biochem J 2009,417(1),1-13

Subramaniam S.R.; Chesselet M.F.; Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 2013,106-107,17-32

Hauser D.N.; Hastings T.G.; Mitochondrial dysfunction and oxidative stress in Parkinson’s disease and monogenic parkinsonism. Neurobiol Dis 2013,51,35-42

Mann V.M.; Cooper J.M.; Daniel S.E.; Complex I, iron, and ferritin in Parkinson’s disease substantia nigra. Ann Neurol 1994,36(6),876-881

Parker W.D.; Parks J.K.; Swerdlow R.H.; Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 2008,1189,215-218

Valsecchi F.; Koopman W.J.; Manjeri G.R.; Rodenburg R.J.; Smeitink J.A.; Willems P.H.; Complex I disorders: causes, mechanisms, and development of treatment strategies at the cellular level. Dev Disabil Res Rev 2010,16(2),175-182

Li N.; Ragheb K.; Lawler G.; Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem 2003,278(10),8516-8525

Przedborski S.; Tieu K.; Perier C.; Vila M.; MPTP as a mitochondrial neurotoxic model of Parkinson’s disease. J Bioenerg Biomembr 2004,36(4),375-379

Dranka B.P.; Zielonka J.; Kanthasamy A.G.; Kalyanaraman B.; Alterations in bioenergetic function induced by Parkinson’s disease mimetic compounds: lack of correlation with superoxide generation. J Neurochem 2012,122(5),941-951

Zawada W.M.; Banninger G.P.; Thornton J.; 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

Votyakova T.V.; Reynolds I.J.; Ca-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I. J Neurochem 2005,93(3),526-537

Palacino J.J.; Sagi D.; Goldberg M.S.; Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 2004,279(18),18614-18622

Gegg M.E.; Cooper J.M.; Schapira A.H.; Taanman J.W.; Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One 2009,4(3)

Gautier C.A.; 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),11364-11369

Ziviani E.; Tao R.N.; Whitworth A.J.; Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA 2010,107(11),5018-5023

Jiang H.; Ren Y.; Zhao J.; Feng J.; Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis. Hum Mol Genet 2004,13(16),1745-1754

Wood-Kaczmar A.; Gandhi S.; Yao Z.; PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS One 2008,3(6)

Amo T.; Sato S.; Saiki S.; 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),111-118

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

Deas E.; Wood N.W.; Plun-Favreau H.; Mitophagy and Parkinson’s disease: the PINK1-parkin link. Biochim Biophys Acta 2011,1813(4),623-633

Vives-Bauza C.; Zhou C.; Huang Y.; PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA 2010,107(1),378-383

Narendra D.P.; Jin S.M.; Tanaka A.; PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010,8(1)

de Vries R.L.A.; Przedborski S.; Mitophagy and Parkinson’s disease: be eaten to stay healthy. Mol Cell Neurosci 2013,55,37-43

Michel P.P.; Hirsch E.C.; Hunot S.; Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron 2016,90(4),675-691

Kelsey N.A.; Wilkins H.M.; Linseman D.A.; Nutraceutical antioxidants as novel neuroprotective agents. Molecules 2010,15(11),7792-7814

Ebrahimi A.; Schluesener H.; Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing Res Rev 2012,11(2),329-345

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-S120

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),651-668

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),719-735

DeFeudis F.V.; Drieu K.; Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets 2000,1(1),25-58

Pardon M.C.; Joubert C.; Perez-Diaz F.; Christen Y.; Launay J.M.; 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),157-168

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),1417-1423

Rojas P.; Garduño B.; Rojas C.; EGb761 blocks MPP+-induced lipid peroxidation in mouse corpus striatum. Neurochem Res 2001,26(11),1245-1251

Rojas P.; Ruiz-Sánchez E.; Rojas C.; Ogren S.O.; 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 2012,223,246-257

Rojas P.; Serrano-García N.; Mares-Sámano J.J.; Medina-Campos O.N.; Pedraza-Chaverri J.; Ogren S.O.; 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

Checkoway H.; Powers K.; Smith-Weller T.; Franklin G.M.; Longstreth W.T.; Swanson P.D.; Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002,155(8),732-738

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),2242-2248

Li F.J.; Ji H.F.; Shen L.; A meta-analysis of tea drinking and risk of Parkinson’s disease. Scientific World Journal 2012

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),430-439

Mandel S.A.; Amit T.; Kalfon L.; Reznichenko L.; Youdim M.B.; Targeting multiple neurodegenerative diseases etiologies with multimodal-acting green tea catechins. J Nutr 2008,138(8),1578S-1583S

Levites Y.; Weinreb O.; Maor G.; Youdim M.B.; 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),1073-1082

Choi J.Y.; Park C.S.; Kim D.J.; 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),367-374

Kim J.S.; Kim J.M.; 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),1165-1168

Xu Q.; Langley M.; Kanthasamy A.G.; Reddy M.B.; Epigallocatechin gallate has a neurorescue effect in a mouse model of parkinson disease. J Nutr 2017,147(10),1926-1931

Dai J.; Mumper R.J.; Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 2010,15(10),7313-7352

de Souza R.F.; De Giovani W.F.; Antioxidant properties of complexes of flavonoids with metal ions. Redox Rep 2004,9(2),97-104

van Acker S.A.; van den Berg D.J.; Tromp M.N.; Structural aspects of antioxidant activity of flavonoids. Free Radic Biol Med 1996,20(3),331-342

Grinberg L.N.; Newmark H.; Kitrossky N.; Rahamim E.; Chevion M.; Rachmilewitz E.A.; Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol 1997,54(9),973-978

Jomova K.; Vondrakova D.; Lawson M.; Valko M.; Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 2010,345(1-2),91-104

Mandel S.; Maor G.; Youdim M.B.; 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),401-416

Perron N.R.; Hodges J.N.; Jenkins M.; Brumaghim J.L.; Predicting how polyphenol antioxidants prevent DNA damage by binding to iron. Inorg Chem 2008,47(14),6153-6161

Mounsey R.B.; Teismann P.; Chelators in the treatment of iron accumulation in Parkinson’s disease. Int J Cell Biol 2012

Daniel S.; Limson J.L.; Dairam A.; Watkins G.M.; 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),266-275

Du X.X.; Xu H.M.; Jiang H.; Song N.; Wang J.; Xie J.X.; Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurosci Bull 2012,28(3),253-258

Dai M.C.; Zhong Z.H.; Sun Y.H.; Curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis. Neurosci Lett 2013,536,41-46

Gupta S.C.; Prasad S.; Kim J.H.; Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 2011,28(12),1937-1955

Khatri D.K.; Juvekar A.R.; 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

Harish G.; Venkateshappa C.; Mythri R.B.; 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),2631-2638

Dickinson D.A.; Iles K.E.; Zhang H.; Blank V.; Forman H.J.; Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression. FASEB J 2003,17(3),473-475

Jagatha B.; Mythri R.B.; Vali S.; Bharath M.M.; 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),907-917

Pandareesh M.D.; Shrivash M.K.; Naveen Kumar H.N.; Misra K.; Srinivas Bharath M.M.; Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson’s Disease. Neurochem Res 2016,41(11),3113-3128

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

Tanaka K.; Galduróz R.F.; Gobbi L.T.; Galduróz J.C.; Ginkgo biloba extract in an animal model of Parkinson’s disease: a systematic review. Curr Neuropharmacol 2013,11(4),430-435

Ahmad M.; Saleem S.; Ahmad A.S.; 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

Tellone E.; Galtieri A.; Russo A.; Giardina B.; Ficarra S.; Resveratrol: A focus on several neurodegenerative diseases. Oxid Med Cell Longev 2015

Fukui M.; Choi H.J.; Zhu B.T.; Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death. Free Radic Biol Med 2010,49(5),800-813

Moldzio R.; Radad K.; Krewenka C.; Kranner B.; Duvigneau J.C.; Rausch W.D.; Protective effects of resveratrol on glutamate-induced damages in murine brain cultures. J Neural Transm (Vienna) 2013,120(9),1271-1280

Lagouge M.; Argmann C.; Gerhart-Hines Z.; Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 2006,127(6),1109-1122

Wu Y.; Li X.; Zhu J.X.; Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals 2011,19(3),163-174

Lin T-K.; Chen S-D.; Chuang Y-C.; 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),1625-1646

Ferretta A.; Gaballo A.; Tanzarella P.; Effect of resveratrol on mitochondrial function: implications in parkin-associated familiar Parkinson’s disease. Biochim Biophys Acta 2014,1842(7),902-915

Mathieu L.; Lopes Costa A.; Le Bachelier C.; Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3. Free Radic Biol Med 2016,96,190-198

Peng K, Tao Y, Zhang J, et al. Resveratrol regulates mitochondrial biogenesis and fission/fusion to attenuate rotenone-induced neurotoxicity. 2015; 2015

Boots A.W.; Haenen G.R.M.M.; Bast A.; Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 2008,585(2-3),325-337

Karuppagounder S.S.; Madathil S.K.; Pandey M.; Haobam R.; Rajamma U.; Mohanakumar K.P.; Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience 2013,236,136-148

Sharma D.R.; Wani W.Y.; Sunkaria A.; Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus. Neuroscience 2016,324,163-176

Ay M.; Luo J.; Langley M.; 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),766-782

Singh N.; Haldar S.; Tripathi A.K.; Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal 2014,20(8),1324-1363

Kandinov B.; Giladi N.; Korczyn A.D.; Smoking and tea consumption delay onset of Parkinson’s disease. Parkinsonism Relat Disord 2009,15(1),41-46

Pasinetti G.M.; 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),1202-1208

Colizzi C.; The protective effects of polyphenols on Alzheimer’s disease: A systematic review. Alzheimers Dement (N Y) 2018,5,184-196

Baum L.; Lam C.W.; Cheung S.K.; Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008,28(1),110-113

Turner R.S.; Thomas R.G.; Craft S.; A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 2015,85(16),1383-1391

Moussa C.; Hebron M.; Huang X.; Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation 2017,14(1),1

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),716-723

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

Maclennan K.M.; Darlington C.L.; Smith P.F.; The CNS effects of Ginkgo biloba extracts and ginkgolide B. Prog Neurobiol 2002,67(3),235-257

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),224-229

Ringman J.M.; Frautschy S.A.; Teng E.; 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

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 2014,9,2065-2077

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.

Pagano E.; Romano B.; Izzo A.A.; Borrelli F.; The clinical efficacy of curcumin-containing nutraceuticals: An overview of systematic reviews. Pharmacol Res 2018,134,79-91

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),12183-12199

Molino S.; Dossena M.; Buonocore D.; Polyphenols in dementia: From molecular basis to clinical trials. Life Sci 2016,161,69-77

Barnes S.; Prasain J.; D’Alessandro T.; The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct 2011,2(5),235-244

Figueira I.; Menezes R.; Macedo D.; Costa I.; Dos Santos C.N.; Polyphenols Beyond Barriers: A Glimpse into the Brain. Curr Neuropharmacol 2017,15(4),562-594

Youdim K.A.; Shukitt-Hale B.; Joseph J.A.; 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),1683-1693

Renaud J.; Martinoli M.G.; Considerations for the Use of Polyphenols as Therapies in neurodegenerative diseases. Int J Mol Sci 2019,20(8),1883

Kujawska M.; Jodynis-Liebert J.; Polyphenols in parkinson’s disease: A systematic review of in vivo studies. Nutrients 2018,10(5),642

Modi G.; Pillay V.; Choonara Y.E.; Advances in the treatment of neurodegenerative disorders employing nanotechnology. Ann N Y Acad Sci 2010,1184,154-172

Sandhir R.; Yadav A.; Sunkaria A.; Singhal N.; Nano-antioxidants: An emerging strategy for intervention against neurodegenerative conditions. Neurochem Int 2015,89,209-226

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

da Rocha Lindner G.; Bonfanti Santos D.; Colle D.; Improved neuroprotective effects of resveratrol-loaded polysorbate 80-coated poly(lactide) nanoparticles in MPTP-induced Parkinsonism. Nanomedicine (Lond) 2015,10(7),1127-1138

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),445-453

Pandita D.; Kumar S.; Poonia N.; Lather V.; Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol. Food Res Int 2014,62,1165-1174

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 2018,112,239-254

Bollimpelli V.S.; Kumar P.; Kumari S.; Kondapi A.K.; Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity. Neurochem Int 2016,95,37-45

Kanai M.; Imaizumi A.; Otsuka Y.; 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

Dos Santos M.C.T.; Scheller D.; Schulte C.; Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis. PLoS One 2018,13(11)

Miller D.B.; O’Callaghan J.P.; Biomarkers of Parkinson’s disease: present and future. Metabolism 2015,64(3)(Suppl. 1),S40-S46

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

Mollenhauer B.; Caspell-Garcia C.J.; Coffey C.S.; Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology 2017,89(19),1959-1969

Sharma S.; Moon C.S.; Khogali A.; Biomarkers in Parkinson’s disease (recent update). Neurochem Int 2013,63(3),201-229

Ide K.; Yamada H.; Umegaki K.; Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson’s disease. Nutrition 2015,31(2),406-408

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

Lotankar S.; Prabhavalkar K.S.; Bhatt L.K.; Biomarkers for parkinson’s disease: recent advancement. Neurosci Bull 2017,33(5),585-597

Lin X.; Cook T.J.; Zabetian C.P.; DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep 2012,2,954

Saito Y.; Oxidized DJ-1 as a possible biomarker of Parkinson’s disease. J Clin Biochem Nutr 2014,54(3),138-144

Shen L.; Ji H-F.; Low uric acid levels in patients with Parkinson’s disease: evidence from meta-analysis. BMJ Open 2013,3(11)

Wen M.; Zhou B.; Chen Y.H.; Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis. PLoS One 2017,12(3)

Boots AW, Haenen GRMM, Bast A. Health effects of quercetin: From antioxidant to nutraceutical. 2008; 325-7.

Murakami A.; Dose-dependent functionality and toxicity of green tea polyphenols in experimental rodents. Arch Biochem Biophys 2014,557,3-10

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 2018,95,412-433