Generic placeholder image

Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article (Mini-Review)

The Therapeutic Potential of Quercetin in Parkinson’s Disease: Insights into its Molecular and Cellular Regulation

Author(s): Omid Reza Tamtaji, Tooba Hadinezhad, Maryam Fallah, Arash Rezaei Shahmirzadi, Mohsen Taghizadeh, Mohammad Behnam and Zatollah Asemi*

Volume 21 , Issue 5 , 2020

Page: [509 - 518] Pages: 10

DOI: 10.2174/1389450120666191112155654

Price: $65


Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.

Keywords: Quercetin, parkinson's disease, dopamine, inflammatory cytokines, apoptosis, autophagy.

Graphical Abstract
Schneider RB, Iourinets J, Richard IH. Parkinson’s disease psychosis: presentation, diagnosis and management. Neurodegener Dis Manag 2017; 7(6): 365-76.
[] [PMID: 29160144]
Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 1991; 114(Pt 5): 2283-301.
[] [PMID: 1933245]
Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord 2019; 34(2): 180-98.
[] [PMID: 30653247]
Tysnes O-B, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna) 2017; 124(8): 901-5.
[] [PMID: 28150045]
Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med 2009; 361(17): 1651-61.
[] [PMID: 19846850]
Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat Rev Neurosci 2010; 11(12): 791-7.
[] [PMID: 21088684]
Song S, Jang S, Park J, et al. Characterization of PINK1 (PTEN-induced putative kinase 1) mutations associated with Parkinson disease in mammalian cells and Drosophila. J Biol Chem 2013; 288(8): 5660-72.
[] [PMID: 23303188]
Lücking CB, Dürr A, Bonifati V, et al. Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 2000; 342(21): 1560-7.
[] [PMID: 10824074]
Canet-Avilés RM, Wilson MA, Miller DW, et al. The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA 2004; 101(24): 9103-8.
[] [PMID: 15181200]
Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 1997; 276(5321): 2045-7.
[] [PMID: 9197268]
Anglade P, Vyas S, Javoy-Agid F, et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 1997; 12(1): 25-31.
[PMID: 9046040]
Mochizuki H, Goto K, Mori H, Mizuno Y. Histochemical detection of apoptosis in Parkinson’s disease. J Neurol Sci 1996; 137(2): 120-3.
[] [PMID: 8782165]
Tamtaji OR, Behnam M, Pourattar MA, Jafarpour H, Asemi Z. Aquaporin 4: A key player in Parkinson’s disease. J Cell Physiol 2019; 234(12): 21471-8.
[] [PMID: 31127615]
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]
Zhang Y, Dawson VL, Dawson TM. Oxidative stress and genetics in the pathogenesis of Parkinson’s disease. Neurobiol Dis 2000; 7(4): 240-50.
[] [PMID: 10964596]
Kim YS, Joh TH. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease. Exp Mol Med 2006; 38(4): 333-47.
[] [PMID: 16953112]
Kouchaki E, Kakhaki RD, Tamtaji OR, et al. Increased serum levels of TNF-α and decreased serum levels of IL-27 in patients with Parkinson disease and their correlation with disease severity. Clin Neurol Neurosurg 2018; 166: 76-9.
[] [PMID: 29408778]
Kouchaki E, Daneshvar Kakhaki R, Tamtaji OR, et al. Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity. Metab Brain Dis 2018; 33(6): 1955-9.
[] [PMID: 30105613]
Tamtaji OR, Taghizadeh M, Daneshvar Kakhaki R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin Nutr 2019; 38(3): 1031-5.
[] [PMID: 29891223]
Tamtaji OR, Kouchaki E, Salami M, et al. The effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr 2017; 36(8): 660-5.
[] [PMID: 28922099]
Tamtaji OR, Mirhosseini N, Reiter RJ, Azami A, Asemi Z. Melatonin, a calpain inhibitor in the central nervous system: Current status and future perspectives. J Cell Physiol 2019; 234(2): 1001-7.
[] [PMID: 30145792]
Mahboubi M, Taghizadeh M, Talaei SA, Takht Firozeh SM, Rashidi AA, Tamtaji OR. Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iran J Psychiatry Behav Sci 2016; 10(3)e681
[] [PMID: 27822272]
Venkatesh Gobi V, Rajasankar S, Swaminathan Johnson WM, Prabu K, Ramkumar M. Antiapoptotic role of Agaricus blazei extract in rodent model of Parkinson’s disease. Front Biosci (Elite Ed) 2019; 11: 12-9.
[] [PMID: 30468634]
Tamtaji OR, Taghizadeh M, Aghadavod E, et al. The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin Neurol Neurosurg 2019; 176: 116-21.
[] [PMID: 30554092]
Schirinzi T, Martella G, Imbriani P, et al. Dietary Vitamin E as a Protective Factor for Parkinson’s Disease: Clinical and Experimental Evidence. Front Neurol 2019; 10: 148.
[] [PMID: 30863359]
Ahmed S, Khan H, Mirzaei H. Mechanics insights of curcumin in myocardial ischemia: Where are we standing? Eur J Med Chem 2019.183111658
[] [PMID: 31514063]
Ghasemi F, Shafiee M, Banikazemi Z, et al. Curcumin inhibits NF-kB and Wnt/β-catenin pathways in cervical cancer cells. Pathol Res Pract 2019; 215(10)152556
[] [PMID: 31358480]
Shafabakhsh R, Pourhanifeh MH, Mirzaei HR, Sahebkar A, Asemi Z, Mirzaei H. Targeting regulatory T cells by curcumin: A potential for cancer immunotherapy. Pharmacol Res 2019.147104353
[] [PMID: 31306775]
Hesari A, Azizian M, Sheikhi A, Nesaei A, Sanaei S, Mahinparvar N, et al. Chemopreventive and therapeutic potential of curcumin in esophageal cancer. Current and future status. Int J Cancer 2019; 144(6): 1215-26.
Mirzaei H, Masoudifar A, Sahebkar A, et al. MicroRNA: A novel target of curcumin in cancer therapy. J Cell Physiol 2018; 233(4): 3004-15.
[] [PMID: 28617957]
Mirzaei H, Khoi MJ, Azizi M, Goodarzi M. Can curcumin and its analogs be a new treatment option in cancer therapy? Cancer Gene Ther 2016; 23(11): 410.
[] [PMID: 27853147]
Akbari M, Tamtaji OR, Lankarani KB, et al. The effects of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. High Blood Press Cardiovasc Prev 2019; 26(4): 305-19.
[] [PMID: 31264084]
Enogieru AB, Haylett W, Hiss DC, Bardien S, Ekpo OE. Rutin as a potent antioxidant: implications for neurodegenerative disorders. Oxid Med Cell Longev 2018.20186241017
[] [PMID: 30050657]
Azevedo MI, Pereira AF, Nogueira RB, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain 2013; 9: 53.
[] [PMID: 24152430]
Morand C, Manach C, Crespy V, Remesy C. Respective bioavailability of quercetin aglycone and its glycosides in a rat model. Biofactors 2000; 12(1-4): 169-74.
[] [PMID: 11216481]
Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci 1999; 65(4): 337-53.
[] [PMID: 10421421]
Emim JA, Oliveira AB, Lapa AJ. Pharmacological evaluation of the anti-inflammatory activity of a citrus bioflavonoid, hesperidin, and the isoflavonoids, duartin and claussequinone, in rats and mice. J Pharm Pharmacol 1994; 46(2): 118-22.
[] [PMID: 8021799]
Ferrándiz ML, Alcaraz MJ. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions 1991; 32(3-4): 283-8.
[] [PMID: 1650522]
Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 2008; 585(2-3): 325-37.
[] [PMID: 18417116]
Williamson G, Plumb GW, Uda Y, Price KR, Rhodes MJ. Dietary quercetin glycosides: antioxidant activity and induction of the anticarcinogenic phase II marker enzyme quinone reductase in Hepalclc7 cells. Carcinogenesis 1996; 17(11): 2385-7.
[] [PMID: 8968052]
Overman A, Chuang CC, McIntosh M. Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media. Int J Obes 2011; 35(9): 1165-72.
[] [PMID: 21224828]
Liu C-M, Zheng Y-L, Lu J, et al. Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environ Toxicol Pharmacol 2010; 29(2): 158-66.
[] [PMID: 21787598]
Careri M, Corradini C, Elviri L, Nicoletti I, Zagnoni I. Direct HPLC analysis of quercetin and trans-resveratrol in red wine, grape, and winemaking byproducts. J Agric Food Chem 2003; 51(18): 5226-31.
[] [PMID: 12926863]
Olthof MR, Hollman PC, Buijsman MN, van Amelsvoort JM, Katan MB. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 2003; 133(6): 1806-14.
[] [PMID: 12771321]
Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem 2008; 108(3): 879-84.
[] [PMID: 26065748]
Monori-Kiss A, Monos E, Nádasy GL. Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro. PLoS One 2014; 9(8)e105587
[] [PMID: 25144688]
Larson AJ, Symons JD, Jalili T. Quercetin: a treatment for hypertension?-a review of efficacy and mechanisms. Pharmaceuticals (Basel) 2010; 3(1): 237-50.
[] [PMID: 27713250]
Ożarowski M, Mikołajczak PL, Kujawski R, et al. Pharmacological effect of quercetin in hypertension and its potential application in pregnancy-induced hypertension: review of in vitro, in vivo, and clinical studies. Evid Based Complement Alternat Med 2018.20187421489
[] [PMID: 30622610]
Sternberg Z, Chadha K, Lieberman A, et al. Quercetin and interferon-β modulate immune response(s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients. J Neuroimmunol 2008; 205(1-2): 142-7.
[] [PMID: 18926575]
Nassiri-Asl M, Hajiali F, Taghiloo M, Abbasi E, Mohseni F, Yousefi F. Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models. Toxicol Ind Health 2016; 32(5): 936-44.
[] [PMID: 24442347]
Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer’s disease. J Nutr Biochem 2009; 20(4): 269-75.
[] [PMID: 18602817]
Sabogal-Guáqueta AM, Muñoz-Manco JI, Ramírez-Pineda JR, Lamprea-Rodriguez M, Osorio E, Cardona-Gómez GP. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 2015; 93: 134-45.
[] [PMID: 25666032]
Ahn T-B, Jeon BS. The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein. Neural Regen Res 2015; 10(7): 1113-9.
[] [PMID: 26330835]
Singh S, Jamwal S, Kumar P. Neuroprotective potential of Quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. Neural Regen Res 2017; 12(7): 1137-44.
[] [PMID: 28852397]
Mu X, Yuan X, Du L-D, He G-R, Du G-H. Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats. J Asian Nat Prod Res 2016; 18(1): 65-71.
[] [PMID: 26217978]
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.
[] [PMID: 28376279]
Ghaffari F, Hajizadeh Moghaddam A, Zare M. Neuroprotective Effect of Quercetin Nanocrystal in a 6-Hydroxydopamine Model of Parkinson Disease: Biochemical and Behavioral Evidence. Basic Clin Neurosci 2018; 9(5): 317-24.
[] [PMID: 30719246]
Kääriäinen TM, Piltonen M, Ossola B, et al. Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine-induced parkinsonian models in rats and dopaminergic cell cultures. Brain Res 2008; 1203: 149-59.
[] [PMID: 18329008]
Valentová K, Vrba J, Bancířová M, Ulrichová J, Křen V. Isoquercitrin: pharmacology, toxicology, and metabolism. Food Chem Toxicol 2014; 68: 267-82.
[] [PMID: 24680690]
Vellosa JCR, Regasini LO, Khalil NM. Antioxidant and cytotoxic studies for kaempferol, quercetin and isoquercitrin. Eclética Quimica 2011; 36(2): 07-20.
Rogerio AP, Kanashiro A, Fontanari C, et al. Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflamm Res 2007; 56(10): 402-8.
[] [PMID: 18026696]
Zhu M, Li J, Wang K, Hao X, Ge R, Li Q. Isoquercitrin inhibits hydrogen peroxide-induced apoptosis of EA. hy926 cells via the PI3K/Akt/GSK3β signaling pathway. Molecules 2016; 21(3): 356.
[] [PMID: 27007368]
Carmona V, Martín-Aragón S, Goldberg J, Schubert D, Bermejo-Bescós P. Several targets involved in Alzheimer’s disease amyloidogenesis are affected by morin and isoquercitrin. Nutr Neurosci 2018; 1-16.
[] [PMID: 30326823]
Magalingam KB, Radhakrishnan A, Ramdas P, Haleagrahara N. Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson’s disease. J Mol Neurosci 2015; 55(3): 609-17.
[] [PMID: 25129099]
Magalingam KB, Radhakrishnan A, Haleagrahara N. Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells. Int J Immunopathol Pharmacol 2016; 29(1): 30-9.
[] [PMID: 26542606]
Ibáñez P, Bonnet AM, Débarges B, et al. Causal relation between α-synuclein gene duplication and familial Parkinson’s disease. Lancet 2004; 364(9440): 1169-71.
[] [PMID: 15451225]
Flower TR, Chesnokova LS, Froelich CA, Dixon C, Witt SN. Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson’s disease. J Mol Biol 2005; 351(5): 1081-100.
[] [PMID: 16051265]
Masliah E, Rockenstein E, Veinbergs I, et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 2000; 287(5456): 1265-9.
[] [PMID: 10678833]
Alvarez-Erviti L, Couch Y, Richardson J, Cooper JM, Wood MJ. Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neurosci Res 2011; 69(4): 337-42.
[] [PMID: 21255620]
Zhu M, Han S, Fink AL. Oxidized quercetin inhibits α-synuclein fibrillization. Biochimica et Biophysica Acta (BBA)-. General Subjects 2013; 1830(4): 2872-81.
Boje KM, Arora PK. Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res 1992; 587(2): 250-6.
[] [PMID: 1381982]
Ghoshal A, Das S, Ghosh S, et al. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 2007; 55(5): 483-96.
[] [PMID: 17203475]
Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 2002; 81(6): 1285-97.
[] [PMID: 12068076]
Nair MP, Mahajan S, Reynolds JL, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κ β system. Clin Vaccine Immunol 2006; 13(3): 319-28.
[] [PMID: 16522772]
Rinwa P, Kumar A. Quercetin suppress microglial neuroinflammatory response and induce antidepressent-like effect in olfactory bulbectomized rats. Neuroscience 2013; 255: 86-98.
[] [PMID: 24095694]
Yang J, Kim C-S, Tu TH, et al. Quercetin protects obesity-induced hypothalamic inflammation by reducing microglia-mediated inflammatory responses via HO-1 induction. Nutrients 2017; 9(7): 650.
[] [PMID: 28644409]
Mu X, Yuan X, Du LD, He GR, Du GH. Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats. J Asian Nat Prod Res 2016; 18(1): 65-71.
[] [PMID: 26217978]
Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014; 94(3): 909-50.
[] [PMID: 24987008]
Deas E, Cremades N, Angelova PR, Ludtmann MH, Yao Z, Chen S, et al. Alpha-synuclein oligomers interact with metal ions to induce oxidative stress and neuronal death in Parkinson’s disease. Antioxid Redox Signal 2016; 24(7): 376-91.
Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis: an international journal on programmed cell death 2007; 12(5): 913-22.
Leutner S, Eckert A, Müller WE. ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm (Vienna) 2001; 108(8-9): 955-67.
[] [PMID: 11716148]
Yusa T, Crapo JD, Freeman BA. Liposome-mediated augmentation of brain SOD and catalase inhibits CNS O2 toxicity. J Appl Physiol 1984; 57(6): 1674-81.
[] [PMID: 6511542]
Rhee SG, Yang K-S, Kang SW, Woo HA, Chang T-S. Controlled elimination of intracellular H2O2: regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification. Antioxid Redox Signal 2005; 7(5-6): 619-26.
Itoh K, Wakabayashi N, Katoh Y, Ishii T, O'Connor T, Yamamoto M. Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes to cells: devoted to molecular & cellular mechanisms 2003; 8(4): 379-91.
Kubben N, Zhang W, Wang L, et al. Repression of the antioxidant nrf2 pathway in premature aging. Cell 2016; 165(6): 1361-74.
[] [PMID: 27259148]
Kobayashi A, Kang MI, Okawa H, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol 2004; 24(16): 7130-9.
[] [PMID: 15282312]
Wang S-F, Yen J-C, Yin P-H, Chi C-W, Lee H-C. Involvement of oxidative stress-activated JNK signaling in the methamphetamine-induced cell death of human SH-SY5Y cells. Toxicology 2008; 246(2-3): 234-41.
[] [PMID: 18325654]
Quiroz-Baez R, Rojas E, Arias C. Oxidative stress promotes JNK-dependent amyloidogenic processing of normally expressed human APP by differential modification of α-, β- and γ-secretase expression. Neurochem Int 2009; 55(7): 662-70.
[] [PMID: 19560504]
Shi Q, Gibson GE. Up-regulation of the mitochondrial malate dehydrogenase by oxidative stress is mediated by miR-743a. J Neurochem 2011; 118(3): 440-8.
[] [PMID: 21623795]
Rezaei-Sadabady R, Eidi A, Zarghami N, Barzegar A. Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes. Artif Cells Nanomed Biotechnol 2016; 44(1): 128-34.
[] [PMID: 24959911]
Arredondo F, Echeverry C, Abin-Carriquiry JA, et al. After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med 2010; 49(5): 738-47.
[] [PMID: 20554019]
Saw CL, Guo Y, Yang AY, Paredes-Gonzalez X, Ramirez C, Pung D, et al. The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE signaling pathway. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 2014; 72: 303-11.
Denny Joseph KM. Muralidhara. Combined oral supplementation of fish oil and quercetin enhances neuroprotection in a chronic rotenone rat model: relevance to Parkinson’s disease. Neurochem Res 2015; 40(5): 894-905.
[] [PMID: 25687767]
Haleagrahara N, Siew CJ, Ponnusamy K. Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats. J Toxicol Sci 2013; 38(1): 25-33.
[] [PMID: 23358137]
Haleagrahara N, Siew CJ, Mitra NK, Kumari M. Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum. Neurosci Lett 2011; 500(2): 139-43.
[] [PMID: 21704673]
Magalingam KB, Radhakrishnan A, Haleagrahara N. Protective effects of flavonol isoquercitrin, against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells. BMC Res Notes 2014; 7: 49.
[] [PMID: 24443837]
Hirsch EC, Hunot S, Faucheux B, et al. Dopaminergic neurons degenerate by apoptosis in Parkinson’s disease. Mov Disord 1999; 14(2): 383-5.
[<383:AID-MDS1037>3.0.CO;2-F] [PMID: 10091646]
Salminen A, Ojala J, Kaarniranta K. Apoptosis and aging: increased resistance to apoptosis enhances the aging process. Cell Mol Life Sci 2011; 68(6): 1021-31.
[] [PMID: 21116678]
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35(4): 495-516.
[] [PMID: 17562483]
Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2002; 2(6): 420-30.
[] [PMID: 12189384]
Tsao DH, McDonagh T, Telliez J-B, et al. Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway. Mol Cell 2000; 5(6): 1051-7.
[] [PMID: 10911999]
Hsu H, Shu H-B, Pan M-G, Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 1996; 84(2): 299-308.
[] [PMID: 8565075]
Friesen C, Herr I, Krammer PH, Debatin K-M. Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med 1996; 2(5): 574-7.
[] [PMID: 8616718]
Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58(23): 5315-20.
[PMID: 9850056]
Rytömaa M, Martins LM, Downward J. Involvement of FADD and caspase-8 signalling in detachment-induced apoptosis. Curr Biol 1999; 9(18): 1043-6.
[] [PMID: 10508619]
Yang J, Liu X, Bhalla K, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 1997; 275(5303): 1129-32.
[] [PMID: 9027314]
Rossé T, Olivier R, Monney L, et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 1998; 391(6666): 496-9.
[] [PMID: 9461218]
Tudor G, Gutierrez P, Aguilera-Gutierrez A, Sausville EA. Cytotoxicity and apoptosis of benzoquinones: redox cycling, cytochrome c release, and BAD protein expression. Biochem Pharmacol 2003; 65(7): 1061-75.
[] [PMID: 12663042]
Wang Y, Kim NS, Haince J-F, et al. Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal 2011; 4(167): ra20. [-ra.].
[] [PMID: 21467298]
Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 1991; 67(5): 879-88.
[] [PMID: 1835668]
Hong SJ, Dawson TM, Dawson VL. Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling. Trends Pharmacol Sci 2004; 25(5): 259-64.
[] [PMID: 15120492]
Soengas MS, Alarcón RM, Yoshida H, et al. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 1999; 284(5411): 156-9.
[] [PMID: 10102818]
Li LY, Luo X, Wang X. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 2001; 412(6842): 95-9.
[] [PMID: 11452314]
Yuste VJ, Sánchez-López I, Solé C, et al. The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated DNase to the nuclear phenotype and DNA degradation during apoptosis. J Biol Chem 2005; 280(42): 35670-83.
[] [PMID: 16049016]
Yao R-Q, Qi D-S, Yu H-L, Liu J, Yang L-H, Wu X-X. Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway. Neurochem Res 2012; 37(12): 2777-86.
[] [PMID: 22936120]
Kanter M, Unsal C, Aktas C, Erboga M. Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol Ind Health 2016; 32(3): 541-50.
[] [PMID: 24193051]
Bureau G, Longpré F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res 2008; 86(2): 403-10.
[] [PMID: 17929310]
Cho J-Y, Kim I-S, Jang Y-H, Kim A-R, Lee S-R. Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. Neurosci Lett 2006; 404(3): 330-5.
[] [PMID: 16806698]
Unsal C, Kanter M, Aktas C, Erboga M. Role of quercetin in cadmium-induced oxidative stress, neuronal damage, and apoptosis in rats. Toxicol Ind Health 2015; 31(12): 1106-15.
[] [PMID: 23645211]
Bournival J, Quessy P, Martinoli M-G. Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Mol Neurobiol 2009; 29(8): 1169-80.
[] [PMID: 19466539]
Kuma A, Mizushima N, Eds. Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism Seminars in cell & developmental biology. Elsevier 2010.
Hou X, Hu Z, Xu H, et al. Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway. Cardiovasc Diabetol 2014; 13(1): 78.
[] [PMID: 24725502]
Wu Y-T, Tan H-L, Huang Q, Ong C-N, Shen H-M. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy. Autophagy 2009; 5(6): 824-34.
[] [PMID: 19556857]
Lum JJ, Bauer DE, Kong M, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005; 120(2): 237-48.
[] [PMID: 15680329]
Hemmings BA, Restuccia DF. PI3K-PKB/Akt pathway. Cold Spring Harb Perspect Biol 2012; 4(9)a011189
[] [PMID: 22952397]
Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 2014; 26(12): 2694-701.
[] [PMID: 25173700]
Inoki K, Li Y, Zhu T, Wu J, Guan K-L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4(9): 648-57.
[] [PMID: 12172553]
Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003; 13(15): 1259-68.
[] [PMID: 12906785]
Spilman P, Podlutskaya N, Hart MJ, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-β levels in a mouse model of Alzheimer’s disease. PLoS One 2010; 5(4)e9979
[] [PMID: 20376313]
Marquez RT, Xu L. Bcl-2: Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res 2012; 2(2): 214-21.
[PMID: 22485198]
Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122(6): 927-39.
[] [PMID: 16179260]
Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115(5): 577-90.
[] [PMID: 14651849]
Janda E, Isidoro C, Carresi C, Mollace V. Defective autophagy in Parkinson’s disease: role of oxidative stress. Mol Neurobiol 2012; 46(3): 639-61.
[] [PMID: 22899187]
Arduíno DM, Esteves AR, Cardoso SM. Mitochondrial fusion/ fission, transport and autophagy in Parkinson's disease: when mitochondria get nasty. Parkinson’s Disease 2011 2011.
Spencer B, Potkar R, Trejo M, et al. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson’s and Lewy body diseases. J Neurosci 2009; 29(43): 13578-88.
[] [PMID: 19864570]
El-Horany HE, El-Latif RNA, ElBatsh MM, Emam MN. Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of Parkinson’s disease: modulating autophagy (quercetin on experimental Parkinson’s disease). J Biochem Mol Toxicol 2016; 30(7): 360-9.
[] [PMID: 27252111]
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307(5712): 1098-101.
[] [PMID: 15718470]
Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91(2): 231-41.
[] [PMID: 9346240]
Gardai SJ, Hildeman DA, Frankel SK, et al. Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils. J Biol Chem 2004; 279(20): 21085-95.
[] [PMID: 14766748]
Shimoke K, Chiba H. Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspase-3-like activity using PC12 cells: relevance to therapeutical application for Parkinson’s disease. J Neurosci Res 2001; 63(5): 402-9.
[<402:AID-JNR1035>3.0.CO;2-F] [PMID: 11223915]
Vázquez de la Torre A, Junyent F, Folch J, et al. PI3 k/akt inhibition induces apoptosis through p38 activation in neurons. Pharmacol Res 2013; 70(1): 116-25.
[] [PMID: 23376356]
Timmons S, Coakley MF, Moloney AM, O’ Neill C. Akt signal transduction dysfunction in Parkinson’s disease. Neurosci Lett 2009; 467(1): 30-5.
[] [PMID: 19800394]
Scatton B, Rouquier L, Javoy-Agid F, Agid Y. Dopamine deficiency in the cerebral cortex in Parkinson disease. Neurology 1982; 32(9): 1039-40.
[] [PMID: 7202156]
Johansson B, Roos B-E. 5-hydroxyindoleacetic and homovanillic acid levels in the cerebrospinal fluid of healthy volunteers and patients with Parkinson’s syndrome. Life Sci 1967; 6(13): 1449-54.
[] [PMID: 6035772]
Goldstein DS, Holmes C, Sullivan P, Jinsmaa Y, Kopin IJ, Sharabi Y. Elevated cerebrospinal fluid ratios of cysteinyl-dopamine/3,4-dihydroxyphenylacetic acid in parkinsonian synucleinopathies. Parkinsonism Relat Disord 2016; 31: 79-86.
[] [PMID: 27474472]
Emir UE, Tuite PJ, Öz G. Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. PLoS One 2012; 7(1)e30918
[] [PMID: 22295119]
Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S. Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol Aging 2007; 28(4): 568-78.
[] [PMID: 16563567]
Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic Res 2005; 39(10): 1119-25.
[] [PMID: 16298737]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy