Neuroprotection of Rotenone-Induced Parkinsonism by Ursolic Acid in PD Mouse Model

Author(s): Walia Zahra, Sachchida Nand Rai, Hareram Birla, Saumitra Sen Singh, Aaina Singh Rathore, Hagera Dilnashin, Richa Singh, Chetan Keswani, Rakesh K. Singh, Surya Pratap Singh*

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 19 , Issue 7 , 2020


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Graphical Abstract:


Abstract:

Background: Parkinson’s Disease (PD) is characterized by both motor and non-motor symptoms. The presynaptic neuronal protein, α-Synuclein, plays a pivotal role in PD pathogenesis and is associated with both genetic and sporadic origin of the disease. Ursolic Acid (UA) is a well-known bioactive compound found in various medicinal plants, widely studied for its anti-inflammatory and antioxidant activities.

Objective: In this research article, the neuroprotective potential of UA has been further explored in the Rotenone-induced mouse model of PD.

Methods: To investigate our hypothesis, we have divided mice into 4 different groups, control, drug only control, Rotenone-intoxicated group, and Rotenone-intoxicated mice treated with UA. After the completion of dosing, behavioral parameters were estimated. Then mice from each group were sacrificed and the brains were isolated. Further, the biochemical tests were assayed to check the balance between the oxidative stress and endogenous anti-oxidants; and TH (Tyrosine Hydroxylase), α-Synuclein, Akt (Serine-threonine protein kinase), ERK (Extracellular signal-regulated kinase) and inflammatory parameters like Nuclear Factor-κB (NF-κB) and Tumor Necrosis Factor- α (TNF-α) were assessed using Immunohistochemistry (IHC). Western blotting was also done to check the expressions of TH and α-Synuclein. Moreover, the expression levels of PD related genes like α-Synuclein, β-Synuclein, Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were assessed by using Real-time PCR.

Results: The results obtained in our study suggested that UA significantly reduced the overexpression of α-Synuclein and regulated the phosphorylation of survival-related kinases (Akt and ERK) apart from alleviating the behavioral abnormalities and protecting the dopaminergic neurons from oxidative stress and neuroinflammation.

Conclusion: Thus, our study shows the neuroprotective potential of UA, which can further be explored for possible clinical intervention.

Keywords: Parkinson`s disease, rotenone, α-synuclein, neuroinflammation, oxidative stress, ursolic acid.

[1]
Migliore L, Coppedè F. Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat Res 2009; 667(1-2): 82-97.
[http://dx.doi.org/10.1016/j.mrfmmm.2008.10.011] [PMID: 19026668]
[2]
Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM. Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 2002; 295(5556): 865-8.
[http://dx.doi.org/10.1126/science.1067389] [PMID: 11823645]
[3]
Feany MB, Bender WW. A Drosophila model of Parkinson’s disease. Nature 2000; 404(6776): 394-8.
[http://dx.doi.org/10.1038/35006074]
[4]
Masliah E, Rockenstein E, Veinbergs I. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000; 287(5456): 1265-9.
[http://dx.doi.org/10.1126/science.287.5456.1265]
[5]
Bhullar KS, Rupasinghe HP. Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxid Med Cell Longev 2013; 2013891748
[http://dx.doi.org/10.1155/2013/891748] [PMID: 23840922]
[6]
Lee J, Jo DG, Park D, Chung HY, Mattson MP. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev 2014; 66(3): 815-68.
[7]
Dzamko N, Zhou J, Huang Y, Halliday GM. Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis. Front Mol Neurosci 2014; 7: 57.
[8]
Cao Q, Qin L, Huang F, et al. Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson’s disease model mice through PI3K/Akt and ERK signaling pathways. Toxicol Appl Pharmacol 2017; 319: 80-90.
[http://dx.doi.org/10.1016/j.taap.2017.01.019] [PMID: 28185818]
[9]
Cheng B, Martinez AA, Morado J, Scofield V, Roberts JL, Maffi SK. Retinoic acid protects against proteasome inhibition associated cell death in SH-SY5Y cells via the AKT pathway. Neurochem Int 2013; 62(1): 31-42.
[http://dx.doi.org/10.1016/j.neuint.2012.10.014] [PMID: 23142153]
[10]
Chen WF, Wu L, Du ZR, et al. Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson’s disease: involvement of PI3K/Akt and MEK/ERK signaling pathways. Phytomedicine 2017; 25: 93-9.
[http://dx.doi.org/10.1016/j.phymed.2016.12.017] [PMID: 28190476]
[11]
Rai SN, Dilnashin H, Birla H, et al. The role of PI3K/Akt and ERK in neurodegenerative disorders. Neurotox Res 2019; 35(3): 775-95.
[http://dx.doi.org/10.1007/s12640-019-0003-y] [PMID: 30707354]
[12]
Hashimoto M, Takenouchi T, Rockenstein E, Masliah E. α-synuclein up-regulates expression of caveolin-1 and down-regulates extracellular signal-regulated kinase activity in B103 neuroblastoma cells: role in the pathogenesis of Parkinson’s disease. J Neurochem 2003; 85(6): 1468-79.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01791.x] [PMID: 12787066]
[13]
Hashimoto M, Bar-On P, Ho G, et al. β-synuclein regulates Akt activity in neuronal cells. A possible mechanism for neuroprotection in Parkinson’s disease. J Biol Chem 2004; 279(22): 23622-9.
[http://dx.doi.org/10.1074/jbc.M313784200] [PMID: 15026413]
[14]
Iwata A, Maruyama M, Kanazawa I, Nukina N. α-Synuclein affects the MAPK pathway and accelerates cell death. J Biol Chem 2001; 276(48): 45320-9.
[http://dx.doi.org/10.1074/jbc.M103736200] [PMID: 11560921]
[15]
Ojha S, Javed H, Azimullah S, Abul Khair SB, Haque ME. Neuroprotective potential of ferulic acid in the rotenone model of Parkinson’s disease. Drug Des Devel Ther 2015; 9: 5499-510.
[PMID: 26504373]
[16]
Zhang ZN, Zhang JS, Xiang J, et al. Subcutaneous rotenone rat model of Parkinson’s disease: dose exploration study. Brain Res 2017; 1655: 104-13.
[http://dx.doi.org/10.1016/j.brainres.2016.11.020] [PMID: 27876560]
[17]
Birla H, Rai SN, Singh SS, et al. Tinospora cordifolia suppresses neuroinflammation in parkinsonian mouse model. Neuromolecular Med 2019; 21(1): 42-53.
[http://dx.doi.org/10.1007/s12017-018-08521-7] [PMID: 30644041]
[18]
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]
[19]
Keswani C, Bisen K, Singh SP, Singh HB. Traditional knowledge and medicinal plants of India in intellectual property landscape. Medicinal Plants-International Journal of Phytomedicines and Related Industries 2017; 9(1): 1-1.
[http://dx.doi.org/10.5958/0975-6892.2017.00001.6]
[20]
Rai SN, Birla H, Zahra W, Singh SS, Singh SP. Immunomodulation of Parkinson’s disease using Mucuna pruriens (Mp). J Chem Neuroanat 2017; 85: 27-35.
[http://dx.doi.org/10.1016/j.jchemneu.2017.06.005] [PMID: 28642128]
[21]
Rai SN, Birla H, Singh SS, et al. Mucuna pruriens protects against MPTP Intoxicated Neuroinflammation in Parkinson’s disease through NF-κB/pAKT signaling pathways. Front Aging Neurosci 2017; 9: 421.
[http://dx.doi.org/10.3389/fnagi.2017.00421] [PMID: 29311905]
[22]
Birla H, Keswani C, Rai SN, et al. Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice. Behav Brain Funct 2019; 15(1): 9.
[http://dx.doi.org/10.1186/s12993-019-0160-4] [PMID: 31064381]
[23]
Singh SS, Rai SN, Birla H, et al. Neuroprotective effect of chlorogenic acid on mitochondrial dysfunction-mediated apoptotic death of da neurons in a parkinsonian mouse model. Oxid Med Cell Longev 2020; 20206571484
[http://dx.doi.org/10.1155/2020/6571484]
[24]
Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995; 49(2): 57-68.
[http://dx.doi.org/10.1016/0378-8741(95)90032-2] [PMID: 8847885]
[25]
Neto CC, Amoroso JW, Liberty AM. Anticancer activities of cranberry phytochemicals: an update. Mol Nutr Food Res 2008; 52(S1)(Suppl. 1): S18-27.
[http://dx.doi.org/10.1002/mnfr.200700433] [PMID: 18504707]
[26]
Yamaguchi H, Noshita T, Kidachi Y, et al. Isolation of ursolic acid from apple peels and its specific efficacy as a potent antitumor agent. J Health Sci 2008; 54(6): 654-60.
[http://dx.doi.org/10.1248/jhs.54.654]
[27]
Rai SN, Yadav SK, Singh D, Singh SP. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model. J Chem Neuroanat 2016; 71: 41-9.
[http://dx.doi.org/10.1016/j.jchemneu.2015.12.002] [PMID: 26686287]
[28]
Habtemariam S. Antioxidant and anti-inflammatory mechanisms of neuroprotection by ursolic acid: addressing brain injury, cerebral ischemia, cognition deficit, anxiety, and depression. Oxid Med Cell Longev 2019; 20198512048
[http://dx.doi.org/10.1155/2019/8512048] [PMID: 31223427]
[29]
Zhu Z, Du S, Ding F, Guo S, Ying G, Yan Z. Ursolic acid attenuates temozolomide resistance in glioblastoma cells by downregulating O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Am J Transl Res 2016; 8(7): 3299-308.
[PMID: 27508051]
[30]
Lu J, Wu DM, Zheng YL, et al. Ursolic acid attenuates D-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation. Cereb Cortex 2010; 20(11): 2540-8.
[http://dx.doi.org/10.1093/cercor/bhq002] [PMID: 20133359]
[31]
Wang YJ, Lu J, Wu DM, et al. Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways. Neurobiol Learn Mem 2011; 96(2): 156-65.
[http://dx.doi.org/10.1016/j.nlm.2011.03.010] [PMID: 21496491]
[32]
Manna S, Bhattacharyya D, Mandal TK, Dey S. Neuropharmacological effects of deltamethrin in rats. J Vet Sci 2006; 7(2): 133-6.
[http://dx.doi.org/10.4142/jvs.2006.7.2.133] [PMID: 16645337]
[33]
Pisa M. Regional specialization of motor functions in the rat striatum: implications for the treatment of parkinsonism. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12(2-3): 217-24.
[http://dx.doi.org/10.1016/0278-5846(88)90038-3] [PMID: 3290995]
[34]
Mohanasundari M, Srinivasan MS, Sethupathy S, Sabesan M. Enhanced neuroprotective effect by combination of bromocriptine and Hypericum perforatum extract against MPTP-induced neurotoxicity in mice. J Neurol Sci 2006; 249(2): 140-4.
[http://dx.doi.org/10.1016/j.jns.2006.06.018] [PMID: 16876826]
[35]
Kumar A, Ahmad I, Shukla S, et al. Effect of zinc and paraquat co-exposure on neurodegeneration: modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats. Free Radic Res 2010; 44(8): 950-65.
[http://dx.doi.org/10.3109/10715762.2010.492832] [PMID: 20553223]
[36]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-8.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[37]
Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide -. Biol Chem 2001; 5(1): 62-71.
[38]
Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582(1): 67-78.
[39]
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10): 3170-5.
[PMID: 4623845]
[40]
Gorbatyuk OS, Li S, Sullivan LF, et al. The phosphorylation state of Ser-129 in human α-synuclein determines neurodegeneration in a rat model of Parkinson disease. Proc Natl Acad Sci USA 2008; 105(2): 763-8.
[http://dx.doi.org/10.1073/pnas.0711053105] [PMID: 18178617]
[41]
Peinnequin A, Mouret C, Birot O, et al. Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green. BMC Immunol 2004; 5(1): 3.
[http://dx.doi.org/10.1186/1471-2172-5-3] [PMID: 15040812]
[42]
Gupta SP, Patel S, Yadav S, Singh AK, Singh S, Singh MP. Involvement of nitric oxide in maneb- and paraquat-induced Parkinson’s disease phenotype in mouse: is there any link with lipid peroxidation? Neurochem Res 2010; 35(8): 1206-13.
[http://dx.doi.org/10.1007/s11064-010-0176-5] [PMID: 20455021]
[43]
Normando EM, Davis BM, De Groef L, et al. The retina as an early biomarker of neurodegeneration in a rotenone-induced model of Parkinson’s disease: evidence for a neuroprotective effect of rosiglitazone in the eye and brain. Acta Neuropathol Commun 2016; 4(1): 86.
[http://dx.doi.org/10.1186/s40478-016-0346-z] [PMID: 27535749]
[44]
Anusha C, Sumathi T, Joseph LD. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem Biol Interact 2017; 269: 67-79.
[http://dx.doi.org/10.1016/j.cbi.2017.03.016] [PMID: 28389404]
[45]
Wang H, Dong X, Liu Z, et al. Resveratrol suppresses rotenone‐induced neurotoxicity through activation of SIRT1/Akt1 signaling pathway. Anat Rec (Hoboken) 2018; 301(6): 1115-25.
[http://dx.doi.org/10.1002/ar.23781] [PMID: 29350822]
[46]
Xu Y, Liu C, Chen S, et al. Activation of AMPK and inactivation of Akt result in suppression of mTOR-mediated S6K1 and 4E-BP1 pathways leading to neuronal cell death in in vitro models of Parkinson’s disease. Cell Signal 2014; 26(8): 1680-9.
[http://dx.doi.org/10.1016/j.cellsig.2014.04.009] [PMID: 24726895]
[47]
Jung SY, Lee KW, Choi SM, Yang EJ. Bee venom protects against rotenone-induced cell death in NSC34 motor neuron cells. Toxins 2015; 7(9): 3715-26.
[48]
Song JX, Choi MY, Wong KC, et al. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism. Chin Med 2012; 7(1): 1-9.
[http://dx.doi.org/10.1186/1749-8546-7-1] [PMID: 22264378]
[49]
Luo J, Hu YL, Wang H. Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways in vitro. Exp Ther Med 2017; 14(4): 3623-31.
[http://dx.doi.org/10.3892/etm.2017.4965] [PMID: 29042957]
[50]
Wang X, Zhang F, Yang L, et al. Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. J Biomed Biotechnol 2011; 2011419343
[http://dx.doi.org/10.1155/2011/419343] [PMID: 21716649]
[51]
Wang Y, He Z, Deng S. Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury. Drug Des Devel Ther 2016; 10: 1663-74.
[http://dx.doi.org/10.2147/DDDT.S103829] [PMID: 27274199]
[52]
Machado DG, Neis VB, Balen GO, et al. Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav 2012; 103(2): 204-11.
[http://dx.doi.org/10.1016/j.pbb.2012.08.016] [PMID: 22940588]
[53]
Li L, Zhang X, Cui L, et al. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res 2013; 1497: 32-9.
[http://dx.doi.org/10.1016/j.brainres.2012.12.032] [PMID: 23276496]
[54]
Wilkinson K, Boyd JD, Glicksman M, Moore KJ, El Khoury J. A high content drug screen identifies ursolic acid as an inhibitor of amyloid β protein interactions with its receptor CD36. J Biol Chem 2011; 286(40): 34914-22.
[http://dx.doi.org/10.1074/jbc.M111.232116] [PMID: 21835916]
[55]
Fornai F, Lenzi P, Ferrucci M, et al. Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice. Brain Res Bull 2005; 65(5): 405-13.
[http://dx.doi.org/10.1016/j.brainresbull.2005.02.022] [PMID: 15833595]
[56]
Kowall NW, Hantraye P, Brouillet E, Beal MF, McKee AC, Ferrante RJ. MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons. Neuroreport 2000; 11(1): 211-3.
[http://dx.doi.org/10.1097/00001756-200001170-00041] [PMID: 10683860]
[57]
Di Napoli M, Shah IM, Stewart DA. Molecular pathways and genetic aspects of Parkinson’s disease: from bench to bedside. Expert Rev Neurother 2007; 7(12): 1693-729.
[http://dx.doi.org/10.1586/14737175.7.12.1693] [PMID: 18052765]
[58]
Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature 2009; 458(7242): 1131-5.
[http://dx.doi.org/10.1038/nature07976] [PMID: 19339967]
[59]
Shichiri M. The role of lipid peroxidation in neurological disorders. J Clin Biochem Nutr 2014; 54(3): 151-60.
[http://dx.doi.org/10.3164/jcbn.14-10] [PMID: 24895477]
[60]
Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AH. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 1994; 345(1): 50-4.
[http://dx.doi.org/10.1016/0014-5793(94)00424-2] [PMID: 8194600]
[61]
Friend DM, Fricks-Gleason AN, Keefe KA. Is there a role for nitric oxide in methamphetamine-induced dopamine terminal degeneration? Neurotox Res 2014; 25(2): 153-60.
[http://dx.doi.org/10.1007/s12640-013-9415-2] [PMID: 23918001]
[62]
Tapias V, Hu X, Luk KC, Sanders LH, Lee VM, Greenamyre JT. Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production. Cell Mol Life Sci 2017; 74(15): 2851-74.
[http://dx.doi.org/10.1007/s00018-017-2541-x] [PMID: 28534083]
[63]
Sutachan JJ, Casas Z, Albarracin SL, et al. Cellular and molecular mechanisms of antioxidants in Parkinson’s disease. Nutr Neurosci 2012; 15(3): 120-6.
[http://dx.doi.org/10.1179/1476830511Y.0000000033] [PMID: 22732354]
[64]
Anderson G, Maes M. Neurodegeneration in Parkinson’s disease: interactions of oxidative stress, tryptophan catabolites and depression with mitochondria and sirtuins. Mol Neurobiol 2014; 49(2): 771-83.
[http://dx.doi.org/10.1007/s12035-013-8554-z] [PMID: 24085563]
[65]
Celardo I, Martins LM, Gandhi S. Unravelling mitochondrial pathways to Parkinson’s disease. Br J Pharmacol 2014; 171(8): 1943-57.
[http://dx.doi.org/10.1111/bph.12433] [PMID: 24117181]
[66]
Pigeolet E, Corbisier P, Houbion A, et al. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 1990; 51(3): 283-97.
[http://dx.doi.org/10.1016/0047-6374(90)90078-T] [PMID: 2308398]
[67]
Yuan Y, Sun J, Zhao M, et al. Overexpression of α-synuclein down-regulates BDNF expression. Cell Mol Neurobiol 2010; 30(6): 939-46.
[http://dx.doi.org/10.1007/s10571-010-9523-y] [PMID: 20405200]
[68]
Muhammad T, Ali T, Ikram M, Khan A, Alam SI, Kim MO. Melatonin rescue oxidative stress-mediated neuroinflammation/neurodegeneration and memory impairment in scopolamine-induced amnesia mice model. J Neuroimmune Pharmacol 2019; 14(2): 278-94.
[http://dx.doi.org/10.1007/s11481-018-9824-3] [PMID: 30478761]
[69]
Greene LA, Levy O, Malagelada C. Akt as a victim, villain and potential hero in Parkinson’s disease pathophysiology and treatment. Cell Mol Neurobiol 2011; 31(7): 969-78.
[http://dx.doi.org/10.1007/s10571-011-9671-8] [PMID: 21547489]
[70]
Niranjan R. The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson’s disease: focus on astrocytes. Mol Neurobiol 2014; 49(1): 28-38.
[http://dx.doi.org/10.1007/s12035-013-8483-x] [PMID: 23783559]
[71]
He Q, Yu W, Wu J, et al. Intranasal LPS-mediated Parkinson’s model challenges the pathogenesis of nasal cavity and environmental toxins. PLoS One 2013; 8(11)e78418
[http://dx.doi.org/10.1371/journal.pone.0078418] [PMID: 24250796]
[72]
Zhang W, Yan ZF, Gao JH, et al. Role and mechanism of microglial activation in iron-induced selective and progressive dopaminergic neurodegeneration. Mol Neurobiol 2014; 49(3): 1153-65.
[http://dx.doi.org/10.1007/s12035-013-8586-4] [PMID: 24277523]
[73]
Singh SS, Rai SN, Birla H, Zahra W, Rathore AS, Singh SP. NF-κB-mediated neuroinflammation in Parkinson’s disease and potential therapeutic effect of polyphenols. Neurotox Res 2019; 37(3): 491-507.
[PMID: 31823227]
[74]
Yao K, Zhang L, Zhang Y, Ye P, Zhu N. The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells. Mol Vis 2008; 14: 1865-71.
[PMID: 18949064]
[75]
Al-Rasheed NM, Al-Rasheed NM, Bassiouni YA, et al. Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts. J Physiol Biochem 2015; 71(2): 289-99.
[http://dx.doi.org/10.1007/s13105-015-0412-1] [PMID: 25929726]
[76]
Litteljohn D, Mangano E, Clarke M, Bobyn J, Moloney K, Hayley S. Inflammatory mechanisms of neurodegeneration in toxin-based models of Parkinson’s disease. Parkinsons Dis 2010; 2011713517
[http://dx.doi.org/10.4061/2011/713517] [PMID: 21234362]
[77]
Sherer TB, Betarbet R, Kim JH, Greenamyre JT. Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci Lett 2003; 341(2): 87-90.
[http://dx.doi.org/10.1016/S0304-3940(03)00172-1] [PMID: 12686372]
[78]
Thakur P, Nehru B. Anti-inflammatory properties rather than anti-oxidant capability is the major mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of Parkinson’s disease. Neuroscience 2013; 231: 420-31.
[http://dx.doi.org/10.1016/j.neuroscience.2012.11.006] [PMID: 23159314]
[79]
Singh SS, Rai SN, Birla H, et al. Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse. Front Pharmacol 2018; 9: 757.
[http://dx.doi.org/10.3389/fphar.2018.00757] [PMID: 30127737]
[80]
Yan J, Fu Q, Cheng L, et al. Inflammatory response in Parkinson’s disease. (review) Mol Med Rep 2014; 10(5): 2223-33.
[http://dx.doi.org/10.3892/mmr.2014.2563] [PMID: 25215472]
[81]
Johnson ME, Bobrovskaya L. An update on the rotenone models of Parkinson’s disease: their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology 2015; 46: 101-16.
[http://dx.doi.org/10.1016/j.neuro.2014.12.002] [PMID: 25514659]
[82]
Jiang XW, Qiao L, Feng XX, et al. Rotenone induces nephrotoxicity in rats: oxidative damage and apoptosis. Toxicol Mech Methods 2017; 27(7): 528-36.
[http://dx.doi.org/10.1080/15376516.2017.1333553] [PMID: 28532211]
[83]
Surmeier DJ. α-Synuclein at the synaptic gate. Neuron 2010; 65(1): 3-4.
[http://dx.doi.org/10.1016/j.neuron.2009.12.030] [PMID: 20152107]
[84]
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]
[85]
Michel HE, Tadros MG, Esmat A, Khalifa AE, Abdel-Tawab AM. Tetramethylpyrazine ameliorates rotenone-induced Parkinson’s disease in rats: involvement of its anti-inflammatory and anti-apoptotic actions. Mol Neurobiol 2017; 54(7): 4866-78.
[http://dx.doi.org/10.1007/s12035-016-0028-7] [PMID: 27514753]
[86]
Zhang QS, Heng Y, Yuan YH, Chen NH. Pathological α-synuclein exacerbates the progression of Parkinson’s disease through microglial activation. Toxicol Lett 2017; 265: 30-7.
[http://dx.doi.org/10.1016/j.toxlet.2016.11.002] [PMID: 27865851]
[87]
Goedert M, Spillantini MG, Del Tredici K, Braak H. 100 years of Lewy pathology. Nat Rev Neurol 2013; 9(1): 13-24.
[http://dx.doi.org/10.1038/nrneurol.2012.242] [PMID: 23183883]
[88]
Hoffmann A, Ettle B, Bruno A, et al. Alpha-synuclein activates BV2 microglia dependent on its aggregation state. Biochem Biophys Res Commun 2016; 479(4): 881-6.
[http://dx.doi.org/10.1016/j.bbrc.2016.09.109] [PMID: 27666480]
[89]
Jiang T, Hoekstra J, Heng X, et al. P2X7 receptor is critical in α-synuclein--mediated microglial NADPH oxidase activation. Neurobiol Aging 2015; 36(7): 2304-18.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.03.015] [PMID: 25983062]
[90]
Hoenen C, Gustin A, Birck C, et al. Alpha-synuclein proteins promote pro-inflammatory cascades in microglia: stronger effects of the A53T mutant. PLoS One 2016; 11(9)e0162717
[http://dx.doi.org/10.1371/journal.pone.0162717] [PMID: 27622765]
[91]
Zhang W, Wang T, Pei Z, et al. Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 2005; 19(6): 533-42.
[http://dx.doi.org/10.1096/fj.04-2751com] [PMID: 15791003]
[92]
Wright JA, McHugh PC, Pan S, Cunningham A, Brown DR. Counter-regulation of alpha- and beta-synuclein expression at the transcriptional level. Mol Cell Neurosci 2013; 57: 33-41.
[http://dx.doi.org/10.1016/j.mcn.2013.09.002] [PMID: 24080388]


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Article Details

VOLUME: 19
ISSUE: 7
Year: 2020
Published on: 12 August, 2020
Page: [527 - 540]
Pages: 14
DOI: 10.2174/1871527319666200812224457
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