Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease

Journal of Neuroimmune Pharmacology

Volumn 11, Issue 2, 2016, Pages 259-278

  Ghosh, Anamitra ^a   Langley, Monica R ^a   Harischandra, Dilshan S ^a   Neal, Matthew L ^a   Jin, Huajun ^a   Anantharam, Vellareddy ^a   Joseph, Joy ^b   Brenza, Timothy ^c   Narasimhan, Balaji ^c   Kanthasamy, Arthi ^a   Kalyanaraman, Balaraman ^b   Kanthasamy, Anumantha G ^a  

^a IOWA STATE UNIVERSITY   (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

^c Iowa State University   (United States)

Author keywords

Drug therapy; Microglia; Mito apocynin; Mitochondria; Neuroprotection; Parkinson s disease

Indexed keywords

ACETOPHENONE DERIVATIVE; ANTIOXIDANT; APOCYNIN; AUTACOID; NONSTEROID ANTIINFLAMMATORY AGENT;

ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL CULTURE; CHEMISTRY; DISEASE MODEL; DOPAMINERGIC NERVE CELL; DRUG EFFECTS; INFLAMMATION; MALE; METABOLISM; MITOCHONDRION; MOUSE; NEWBORN; PARKINSONIAN DISORDERS; PATHOLOGY; TREATMENT OUTCOME;

ACETOPHENONES; ANIMALS; ANIMALS, NEWBORN; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIOXIDANTS; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; INFLAMMATION; INFLAMMATION MEDIATORS; MALE; MICE; MICE, INBRED C57BL; MITOCHONDRIA; PARKINSONIAN DISORDERS; TREATMENT OUTCOME;

EID: 84964829444     PISSN: 15571890     EISSN: 15571904     Source Type: Journal    
DOI: 10.1007/s11481-016-9650-4     Document Type: Article

References (88)

1. Anantharam V, Kaul S, Song C, Kanthasamy A, Kanthasamy AG (2007) Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells. Neurotoxicology 28:988–997
2. Ansari MA, Scheff SW (2011) NADPH-oxidase activation and cognition in Alzheimer disease progression. Free Radic Biol Med 51:171–178
3. Ara J, Przedborski S, Naini AB, Jackson-Lewis V, Trifiletti RR, Horwitz J, Ischiropoulos H (1998) Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc Natl Acad Sci U S A 95:7659–7663
4. Athauda D, Foltynie T (2015) The ongoing pursuit of neuroprotective therapies in Parkinson disease. Nat Rev Neurol 11:25–40
5. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313
6. Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR (2015) Oxidative stress and Parkinson’s disease. Front Neuroanat 9:91
7. Block ML, Hong JS (2007) Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem Soc Trans 35:1127–1132
8. Bordt EA, Polster BM (2014) NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair? Free Radic Biol Med 76:34–46
9. Chen S, Le W (2006) Neuroprotective therapy in Parkinson disease. Am J Ther 13:445–457
10. Choi DH, Cristovao AC, Guhathakurta S, Lee J, Joh TH, Beal MF, Kim YS (2012) NADPH oxidase 1-mediated oxidative stress leads to dopamine neuron death in Parkinson’s disease. Antioxid Redox Signal 16:1033–1045
11. Cooney SJ, Bermudez-Sabogal SL, Byrnes KR (2013) Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury. J Neuroinflammation 10:155
12. Cristovao AC, Choi DH, Baltazar G, Beal MF, Kim YS (2009) The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal 11:2105–2118
13. Cristovao AC, Guhathakurta S, Bok E, Je G, Yoo SD, Choi DH, Kim YS (2012) NADPH oxidase 1 mediates alpha-synucleinopathy in Parkinson’s disease. J Neurosci 32:14465–14477
14. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909
15. Dawson TM, Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science (New York. NY 302:819–822
16. Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB (2000) Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 74:2213–2216
17. Dikalov S (2011) Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med 51:1289–1301
18. Dranka BP, Gifford A, Ghosh A, Zielonka J, Joseph J, Kanthasamy AG, Kalyanaraman B (2013) Diapocynin prevents early Parkinson’s disease symptoms in the leucine-rich repeat kinase 2 (LRRK2R(1)(4)(4)(1)G) transgenic mouse. Neurosci Lett 549:57–62
19. Dranka BP, Gifford A, McAllister D, Zielonka J, Joseph J, O’Hara CL, Stucky CL, Kanthasamy AG, Kalyanaraman B (2014) A novel mitochondrially-targeted apocynin derivative prevents hyposmia and loss of motor function in the leucine-rich repeat kinase 2 (LRRK2(R1441G)) transgenic mouse model of Parkinson’s disease. Neurosci Lett 583:159–164
20. Fischer MT, Sharma R, Lim JL, Haider L, Frischer JM, Drexhage J, Mahad D, Bradl M, van Horssen J, Lassmann H (2012) NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain J Neurol 135:886–899
21. Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Tanaka Y, Nakabeppu Y, Noda M (2009) Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One 4:e7247
22. Galea E, Feinstein DL, Reis DJ (1992) Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Proc Natl Acad Sci U S A 89:10945–10949
23. Gao HM, Liu B, Hong JS (2003a) Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 23:6181–6187
24. Gao HM, Liu B, Zhang W, Hong JS (2003b) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956
25. Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM, Ghosh S, Mosley RL, Gendelman HE, Pahan K (2007) Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci U S A 104:18754–18759
26. Ghosh A, Roy A, Matras J, Brahmachari S, Gendelman HE, Pahan K (2009) Simvastatin inhibits the activation of p21ras and prevents the loss of dopaminergic neurons in a mouse model of Parkinson’s disease. J Neurosci 29:13543–13556
27. Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, Kanthasamy A, Kanthasamy A, Kalyanaraman B (2010) Neuroprotection by a mitochondria-targeted drug in a Parkinson’s disease model. Free Radic Biol Med 49:1674–1684
28. Ghosh A, Kanthasamy A, Joseph J, Anantharam V, Srivastava P, Dranka BP, Kalyanaraman B, Kanthasamy AG (2012) Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson’s disease. J Neuroinflammation 9:241
29. Ghosh A, Saminathan H, Kanthasamy A, Anantharam V, Jin H, Sondarva G, Harischandra DS, Qian Z, Rana A, Kanthasamy AG (2013) The peptidyl-prolyl isomerase Pin1 up-regulation and proapoptotic function in dopaminergic neurons: relevance to the pathogenesis of Parkinson disease. J Biol chem 288:21955–21971
30. Goldman SM (2014) Environmental toxins and Parkinson’s disease. Annu Rev Pharmacol Toxicol 54:141–164
31. Gordon R, Hogan CE, Neal ML, Anantharam V, Kanthasamy AG, Kanthasamy A (2011) A simple magnetic separation method for high-yield isolation of pure primary microglia. J Neurosci Methods 194:287–296
32. Grunblatt E, Mandel S, Youdim MB (2000) Neuroprotective strategies in Parkinson’s disease using the models of 6-hydroxydopamine and MPTP. Ann N Y Acad Sci 899:262–273
33. Harraz MM, Marden JJ, Zhou W, Zhang Y, Williams A, Sharov VS, Nelson K, Luo M, Paulson H, Schoneich C, Engelhardt JF (2008) SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest 118:659–670
34. Hayashi T, Juliet PA, Kano-Hayashi H, Tsunekawa T, Dingqunfang D, Sumi D, Matsui-Hirai H, Fukatsu A, Iguchi A (2005) NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent and -independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction. Diabetes, Obes metab 7:334–343
35. Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195–2224
36. Hernandes MS, Santos GD, Cafe-Mendes CC, Lima LS, Scavone C, Munhoz CD, Britto LR (2013) Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration. PLoS One 8:e75532
37. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397
38. Hirsch EC, Vyas S, Hunot S (2012) Neuroinflammation in Parkinson’s disease. Parkinsonism & related disorders 18. Supplement 1:S210–S212
39. Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 72:355–363
40. Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M, Kim H-C, Cass WA, Sullivan PG, Bing G (2007) Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 100:1375–1386
41. Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Bramanti P, Cuzzocrea S (2011) Effect of apocynin, a NADPH oxidase inhibitor, on acute lung inflammation. Biochem Pharmacol 81:636–648
42. Jackson-Lewis V, Przedborski S (2007) Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc 2:141–151
43. Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG (2011) Alpha-synuclein negatively regulates protein kinase cdelta expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. J Neurosci 31:2035–2051
44. Jin H, Kanthasamy A, Ghosh A, Anantharam V, Kalyanaraman B, Kanthasamy AG (2014) Mitochondria-targeted antioxidants for treatment of Parkinson’s disease: preclinical and clinical outcomes. Biochim Biophys Acta 1842:1282–1294
45. Kavanagh E, Rodhe J, Burguillos MA, Venero JL, Joseph B (2014) Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia. Cell Death dis 5:e1565
46. Klingelhoefer L, Reichmann H (2015) Pathogenesis of Parkinson disease[mdash]the gut-brain axis and environmental factors. Nat Rev Neurol 11:625–636
47. Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409
48. Lim HW, In PJ, More SV, Park JY, Kim BW, Jeon SB, Yosep Y, Park EJ, Yoon SH, Choi DK (2015) Anti-neuroinflammatory effects of DPTP, a novel synthetic clovamide derivative in in vitro and in vivo model of neuroinflammation. Brain Res Bull 112:25–34
49. Lofrumento DD, Saponaro C, Cianciulli A, De Nuccio F, Mitolo V, Nicolardi G, Panaro MA (2011) MPTP-induced neuroinflammation increases the expression of pro-inflammatory cytokines and their receptors in mouse brain. Neuroimmunomodulation 18:79–88
50. Luchtefeld R, Luo R, Stine K, Alt ML, Chernovitz PA, Smith RE (2008) Dose formulation and analysis of diapocynin. J Agric Food Chem 56:301–306
51. Maghzal GJ, Krause KH, Stocker R, Jaquet V (2012) Detection of reactive oxygen species derived from the family of NOX NADPH oxidases. Free Radic Biol Med 53:1903–1918
52. McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291
53. Mead EL, Mosley A, Eaton S, Dobson L, Heales SJ, Pocock JM (2012) Microglial neurotransmitter receptors trigger superoxide production in microglia; consequences for microglial-neuronal interactions. J Neurochem 121:287–301
54. Meissner W, Hill MP, Tison F, Gross CE, Bezard E (2004) Neuroprotective strategies for Parkinson’s disease: conceptual limits of animal models and clinical trials. Trends Pharmacol Sci 25:249–253
55. Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C, Gendelman HE (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281
56. Mullin S, Schapira AHV (2015) Pathogenic mechanisms of neurodegeneration in Parkinson disease. Neurol Clin 33:1–17
57. Murakami M, Hirano T (2012) The molecular mechanisms of chronic inflammation development. Front Immunol 3:323
58. Murphy MP (1997) Selective targeting of bioactive compounds to mitochondria. Trends Biotechnol 15:326–330
59. Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Cytokines in Parkinson’s disease. J Neural Transm 143-151
60. Ngwa HA, Kanthasamy A, Jin H, Anantharam V, Kanthasamy AG (2014) Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity. Neurotoxicology 43:73–81
61. Panicker N, Saminathan H, Jin H, Neal M, Harischandra DS, Gordon R, Kanthasamy K, Lawana V, Sarkar S, Luo J, Anantharam V, Kanthasamy AG, Kanthasamy A (2015) Fyn kinase regulates microglial neuroinflammatory responses in cell culture and animal models of Parkinson’s disease. J Neurosci 35:10058–10077
62. Picklo MJ, Amarnath V, McIntyre JO, Graham DG, Montine TJ (1999) 4-hydroxy-2(E)-nonenal inhibits CNS mitochondrial respiration at multiple sites. J Neurochem 72:1617–1624
63. Prediger RD, Aguiar Jr AS, Moreira EL, Matheus FC, Castro AA, Walz R, De Bem AF, Latini A, Tasca CI, Farina M, Raisman-Vozari R (2011) The intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a new rodent model to test palliative and neuroprotective agents for Parkinson’s disease. Curr Pharm Des 17:489–507
64. Przedborski S (2007) Neuroinflammation and Parkinson’s disease. Handb Clin neurol 83:535–551
65. Przedborski S, Tieu K, Perier C, Vila M (2004) MPTP as a mitochondrial neurotoxic model of Parkinson’s disease. J Bioenerg Biomembr 36:375–379
66. Rocha N, de Miranda AS, Teixeira AL (2015) Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti-Inflammatory Based Therapies. BioMed Res Int 2015:12.
67. Sanders LH, McCoy J, Hu X, Mastroberardino PG, Dickinson BC, Chang CJ, Chu CT, Van Houten B, Greenamyre JT (2014) Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson’s disease. Neurobiol Dis 70:214–223
68. Schapira AH, Olanow CW, Greenamyre JT, Bezard E (2014) Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease: future therapeutic perspectives. Lancet 384:545–555
69. Seidl SE, Potashkin JA (2011) The promise of neuroprotective agents in Parkinson’s disease. Front Neurol 2:68
70. Selley ML (1998) (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med 25:169–174
71. Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT (2003) Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 23:10756–10764
72. Smith RA, Porteous CM, Coulter CV, Murphy MP (1999) Selective targeting of an antioxidant to mitochondria. Eur J Biochem/FEBS 263:709–716
73. Sovari AA, Morita N, Karagueuzian HS (2008) Apocynin: a potent NADPH oxidase inhibitor for the management of atrial fibrillation. Redox Report: commun Free Radic Res 13:242–245
74. Stadler K, Bonini MG, Dallas S, Jiang J, Radi R, Mason RP, Kadiiska MB (2008) Involvement of inducible nitric oxide synthase in hydroxyl radical-mediated lipid peroxidation in streptozotocin-induced diabetes. Free Radic Biol Med 45:866–874
75. Strowig T, Henao-Mejia J, Elinav E, Flavell R (2012) Inflammasomes in health and disease. Nature 481:278–286
76. Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37:510–518
77. Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci U S A 100:5473–5478
78. Trumbull KA, McAllister D, Gandelman MM, Fung WY, Lew T, Brennan L, Lopez N, Morre J, Kalyanaraman B, Beckman JS (2012) Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice. Neurobiol Dis 45:137–144
79. Vejrazka M, Micek R, Stipek S (2005) Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells. Biochim Biophys Acta 1722:143–147
80. Vila M, Przedborski S (2004) Genetic clues to the pathogenesis of Parkinson’s disease. Nat Med 10(Suppl):S58–S62
81. Wang WF, Wu SL, Liou YM, Wang AL, Pawlak CR, Ho YJ (2009) MPTP lesion causes neuroinflammation and deficits in object recognition in wistar rats. Behav Neurosci 123:1261–1270
82. Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci U S A 100:6145–6150
83. Wu Y, Le W, Jankovic J (2011) Preclinical biomarkers of Parkinson disease. Arch Neurol 68:22–30
84. Yan J, Fu Q, Cheng L, Zhai M, Wu W, Huang L, Du G (2014) Inflammatory response in Parkinson’s disease (review). Mol Med rep 10:2223–2233
85. Ybot-Gorrin I, Vivancos-Matellano F, Chacon-Pena JR, Alonso-Navarro H, Jimenez-Jimenez FJ (2011) Assessment of Parkinson disease: what do we need to show neuroprotection? Neurologist 17:S21–S29
86. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A 93:2696–2701
87. Zhang D, Anantharam V, Kanthasamy A, Kanthasamy AG (2007) Neuroprotective effect of protein kinase C delta inhibitor rottlerin in cell culture and animal models of Parkinson’s disease. J Pharmacol Exp Ther 322:913–922
88. Zhang FL, He Y, Zheng Y, Zhang WJ, Wang Q, Jia YJ, Song HL, An HT, Zhang HB, Qian YJ, Tong YL, Dong L, Wang XM (2014) Therapeutic effects of fucoidan in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease: role of NADPH oxidase-1. CNS Neurosci Ther 20:1036–1044