Browse > Article
http://dx.doi.org/10.7586/jkbns.2021.23.3.199

Ameliorative Effects of NXP031 on MPTP-Induced Neurotoxicity  

Lee, Joo Hee (College of Nursing Science, Kyung Hee University)
Song, Min Kyung (Robert Wood Johnson Medical School Institute for Neurological Therapeutics, Rutgers Biomedical and Health Sciences, Piscataway, NJRobert Wood Johnson Medical School Institute for Neurological Therapeutics, Rutgers Biomedical and Health Sciences)
Kim, Youn-Jung (College of Nursing Science, Kyung Hee University)
Publication Information
Journal of Korean Biological Nursing Science / v.23, no.3, 2021 , pp. 199-207 More about this Journal
Abstract
Purpose: The purpose of this study was to investigate effects of NXP031, an inhibitor of oxidation by specifically binding to the complex of DNA aptamer/vitamin C, on dopaminergic neurons loss and the reaction of microglia in an animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subchronic Parkinson's disease (PD). Methods: A subchronic PD mouse model was induced via an intraperitoneal (IP) injection of MPTP 30 mg/kg per day for five days. NXP031 (vitamin C/aptamer at 200 mg/4 mg/kg) and vitamin C at 200 mg/kg were administered via IP injections at one hour after performing MPTP injection. This process was performed for five days. Motor function was then evaluated with pole and rotarod tests, after which an immunohistochemical analysis was performed. Results: NXP031 administration after MPTP injection significantly improved motor functions (via both pole and rotarod tests) compared to the control (MPTP injection only) (p<.001). NXP031 alleviated the loss of dopaminergic neurons in the substantia nigra (SN) and striatum caused by MPTP injection. It was found to have a neuroprotective effect by reducing microglia activity. Conclusion: NXP031 can improve impaired motor function, showing neuroprotective effects on dopaminergic neurons in the SN and striatum of MPTP-induced subchronic Parkinson's disease mouse model. Results of this study suggest that NXP031 has potential in future treatments for PD and interventions for nerve recovery.
Keywords
Parkinson disease; Peptide Aptamer; Ascorbic acid; Dopaminergic neuron; Microglia;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Compton DR, Hudzik TJ. Neurochemistry of abuse liability assessment and primary behavioral correlates. In: Carrie G. Markgraf, Thomas J. Hudzik, David R. Compton, Editors. Nonclinical assessment of abuse potential for new pharmaceuticals. 1st ed. Cambridge, MA: Academic Press; 2015. p. 9-48. https://doi.org/10.1016/B978-0-12-420172-9.00002-3
2 Hansen SN, Tveden-Nyborg P, Lykkesfeldt J. Does vitamin C deficiency affect cognitive development and function? Nutrients. 2014;6(9):3818-3846. https://doi.org/10.3390/nu6093818   DOI
3 Seitz G, Gebhardt S, Beck JF, Bohm W, Lode HN, Niethammer D, et al. Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH. Neuroscience Letters. 1998;244(1):33-36. https://doi.org/10.1016/s0304-3940(98)00129-3   DOI
4 Yan J, Studer L, McKay RD. Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors. Journal of Neurochemistry. 2001;76(1):307-311. https://doi.org/10.1046/j.1471-4159.2001.00073.x   DOI
5 Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alpha-synuclein as a therapy for parkinson's disease. Frontiers in Molecular Neuroscience. 2019;12:299. https://doi.org/10.3389/fnmol.2019.00299   DOI
6 Rani L, Sharma N, Singh S, Grewal AS. Therapeutic potential of vitamin c: an overview of various biological activities. International Journal of Pharmaceutical Quality Assurance. 2019;10(04):605-612. https://doi.org/10.25258/ijpqa.10.4.8   DOI
7 Marini AM, Lipsky RH, Schwartz JP, Kopin IJ. Accumulation of 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine in cultured cerebellar astrocytes. Journal of Neurochemistry. 1992;58(4):1250-1258. https://doi.org/10.1111/j.1471-4159.1992.tb11336.x   DOI
8 Watanabe Y, Himeda T, Araki T. Mechanisms of MPTP toxicity and their implications for therapy of parkinson's disease. Medical Science Monitor. 2005;11(1):RA17-23.
9 Andersen JK, Chinta S. Parkinson's disease and aging. In: Sierra F, Kohanski R, editors. Advances in geroscience. 1st ed. Basel: Springer; 2016. P.229-255. https://doi.org/10.1007/978-3-319-23246-1.
10 Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Critical Care. 2014;18(4):460. https://doi.org/10.1186/s13054-014-0460-x   DOI
11 Sun H, Zu Y. A highlight of recent advances in aptamer technology and its application. Molecules. 2015;20(7):11959-11980. https://doi.org/10.3390/molecules200711959   DOI
12 Song MK, Lee JH, Kim J, Kim JH, Hwang S, Kim YS, et al. Neuroprotective effect of NXP031 in the MPTP-induced Parkinson's disease model. Neuroscience Letters. 2021;740:135425. https://doi.org/10.1016/j.neulet.2020.135425   DOI
13 Munoz-Manchado AB, Villadiego J, Romo-Madero S, Suarez-Luna N, Bermejo-Navas A, Rodriguez-Gomez JA, et al. Chronic and progressive parkinson's disease MPTP model in adult and aged mice. Journal of Neurochemistry. 2016;136(2):373-387. https://doi.org/10.1111/jnc.13409   DOI
14 Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979-980. https://doi.org/1126/science.6823561   DOI
15 Tanner CM, Langston JW. Do environmental toxins cause Parkinson's disease? A critical review. Neurology. 1990;40(10 Suppl 3):S17-S30.
16 Trist BG, Hare DJ, Double KL. Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease. Aging Cell. 2019;18(6):e13031. https://doi.org/10.1111/acel.13031   DOI
17 Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003;42(6):1075-1081. https://doi.org/10.1161/01.HYP.0000100443.09293.4F.   DOI
18 Hwang O. Role of oxidative stress in Parkinson's disease. Experimental Neurobiology. 2013;22(1):11-17. https://doi.org/10.5607/en.2013.22.1.11   DOI
19 Das S, Basu A. Inflammation: a new candidate in modulating adult neurogenesis. Journal of Neuroscience Research. 2008;86(6):1199-1208. http://doi:10.1002/jnr.21585   DOI
20 Wang X, Michaelis EK. Selective neuronal vulnerability to oxidative stress in the brain. Frontiers in Aging Neuroscience. 2010;2:12. https://doi.org/10.3389/fnagi.2010.00012   DOI
21 Mallach A, Weinert M, Arthur J, Gveric D, Tierney TS, Alavian KN. Post mortem examination of parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus. FASEB Journal. 2019;33(6):6957-6961. https://doi.org/10.1096/fj.201802628r   DOI
22 Duty S, Jenner P. Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease. British Journal of Pharmacology. 2011;164(4):1357-1391. https://doi.org/10.1111/j.1476-5381.2011.01426.x   DOI
23 Radhakrishnan DM, Goyal V. Parkinson's disease: a review. Neurology India. 2018;66(Suppl):S26-S35. https://doi.org/10.4103/0028-3886.226451.   DOI
24 Santos Garcia D, Labandeira Guerra C, Yanez Bana R, Cimas Hernando MI, Cabo Lopez I, Paz Gonalez JM, et al. Safinamide improves non-motor symptoms burden in parkinson's disease: an open-label prospective study. Brain Sciences. 2021;11(3):316. https://doi.org/10.3390/brainsci11030316.   DOI
25 Lee JE, Choi JK, Lim HS, Kim JH, Cho JH, Kim GS, et al. The prevalence and incidence of parkinson's disease in South Korea: a 10-year nationwide population: Based Study. Journal of the Korean Neurological Association. 2017;35(4):191-198. https://doi.org/10.17340/jkna.2017.4.1   DOI
26 Hallett M. Parkinson's disease tremor: pathophysiology. Parkinsonism Related Disorders. 2012;18 Suppl 1:S85-S86. https://doi.org/10.1016/s1353-8020(11)70027-x   DOI
27 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nature Reviews Disease Primers. 2017;3:17013. https://doi.org/10.1038/nrdp.2017.13   DOI
28 Choi S, Han J, Kim JH, Kim AR, Kim SH, Lee W, et al. Advances in dermatology using DNA aptamer "Aptamin C" innovation: oxidative stress prevention and effect maximization of vitamin C through antioxidation. Journal of Cosmetic Dermatology. 2020;19(4):970-976. https://doi.org/10.1111/jocd.13081   DOI
29 Bornstein SR, Yoshida-Hiroi M, Sotiriou S, Levine M, Hartwig HG, Nussbaum RL, et al. Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2). FASEB Journal. 2003;17(13):1928-1930. https://doi.org/10.1096/fj.02-1167fje   DOI
30 Djuric G, Markovic V, Pekmezovic T, Tomic A, Kresojevic N, Kostic V, et al. Risk factors for levodopa-induced dyskinesia in parkinson's disease patients. Vojnosanitetski Pregled. 2017;74(10):921-926. https://doi.org/10.2298/VSP150723264D   DOI
31 Lyons KE, Pahwa R. Diagnosis and initiation of treatment in parkinson's disease. The International Journal of Neuroscience. 2011;121 Suppl 2:27-36. https://doi.org/10.3109/00207454.2011.620197   DOI
32 Athauda D, Foltynie T. The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in parkinson's disease: mechanisms of action. Drug Discovery Today. 2016;21(5):802-818. https://doi.org/10.1016/j.drudis.2016.01.013   DOI
33 Jang SE, Qiu L, Chan LL, Tan EK, Zeng L. Current status of stem cell-derived therapies for parkinson's disease: from cell assessment and imaging modalities to clinical trials. Frontiers in Neuroscience. 2020;14:558532. https://doi.org/10.3389/fnins.2020.558532   DOI
34 Dawson TM, Ko HS, Dawson VL. Genetic animal models of parkinson's disease. Neuron. 2010;66(5):646-661. https://doi.org/10.1016/j.neuron.2010.04.034   DOI
35 Desole MS, Miele M, Esposito G, Fresu LG, Migheli R, Zangani D, et al. Neuronal antioxidant system and MPTP-induced oxidative stress in the striatum and brain stem of the rat. Pharmacology, Biochemistry, and Behavior. 1995;51(4):581-592. https://doi.org/10.1016/0091-3057(94)00401-4   DOI
36 Glotfelty EJ, Olson L, Karlsson TE, Li Y, Greig NH. Glucagon-like peptide-1 (GLP-1)-based receptor agonists as a treatment for parkinson's disease. Expert Opinion on Investigational Drugs. 2020;29(6):595-602. https://doi.org/10.1080/13543784.2020.1764534.   DOI
37 Grieco M, Giorgi A, Gentile MC, d'Erme M, Morano S, Maras B, Filardi T. Glucagon-like peptide-1: a focus on neurodegenerative diseases. Frontiers in Neuroscience. 2019;13:1112. https://doi.org/10.3389/fnins.2019.01112   DOI
38 Hantikainen E, Trolle Lagerros Y, Ye W, Serafini M, Adami HO, Bellocco R, et al. Dietary antioxidants and the risk of parkinson disease: The Swedish National March Cohort. Neurology. 2021;96(6):e895-e903. https://doi.org/10.1212/WNL.0000000000011373   DOI
39 Choi S, Hwang Y, Kim T, Kim JH. Effects of oxidative stress prevention using DNA aptamer (Aptamin C®) in keratinocyte. Highlights on Medicine and Medical Science. 2021;17:9-16. https://doi.org/10.9734/bpi/hmms/v17/2795F   DOI
40 Mustapha M, Mat Taib CN. MPTP-induced mouse model of Parkinson's disease: a romising direction of therapeutic strategies. Bosnian Journal of Basic Medical Sciences. 2021;21(4):422-433. https://doi.org/10.17305/bjbms.2020.5181   DOI
41 Rice ME. Ascorbate regulation and its neuroprotective role in the brain. Trends in Neurosciencens. 2000;23(5):209-216. https://doi.org/10.1016/s0166-2236(99)01543-x   DOI
42 Smeyne M, Goloubeva O, Smeyne RJ. Strain-dependent susceptibility to MPTP and MPP(+)-induced parkinsonism is determined by glia. Glia. 2001;34(2):73-80.   DOI
43 Acuna AI, Esparza M, Kramm C, Beltran FA, Parra AV, Cepeda C, et al. A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice. Nature Communications. 2013;4:2917. https://doi.org/10.1038/ncomms3917.   DOI
44 Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radical Biology & Medicine. 2009;46(6):719-730. https://doi.org/10.1016/j.freeradbiomed.2008.12.018   DOI
45 Badanjak K, Fixemer S, Smajic S, Skupin A, Grunewald A. The contribution of microglia to neuroinflammation in prkinson's disease. International Journal of Molecular Sciences. 2021;22(9):4676. https://doi.org/10.3390/ijms22094676   DOI
46 Bhaduri B, Abhilash PL, Alladi PA. Baseline striatal and nigral interneuronal protein levels in two distinct mice strains differ in accordance with their MPTP susceptibility. Journal of Chemical Neuroanatomy. 2018;91:46-54. https://doi.org/10.1016/j.jchemneu.2018.04.005   DOI
47 Liebetanz D, Baier PC, Paulus W, Meuer K, Bahr M, Weishaupt JH. A highly sensitive automated complex running wheel test to detect latent motor deficits in the mouse MPTP model of Parkinson's disease. Experimental Neurology. 2007;205(1):207-213. https://doi.org/10.1016/j.expneurol.2007.01.030   DOI