Mitochondrial Dysfunction in Multiple Sclerosis: A Systematic Review
Abstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) and is characterized by a high degree of heterogeneity in progression and treatment response. Mitochondrial dysfunction is increasingly recognized as an important feature of MS pathology and may be relevant for clinical disease progression. This paper systematically reviews published evidence concerning the role of mitochondrial abnormalities with MS. Literature searched using the Web of Science, PMC/Medline via PubMed and Scopus databases up to May 2017 with no time and language limitation. After quality assessment, 9 articles were included in the study. All data extraction was conducted by two reviewers independently. Based on the results of the studies, it seems that mitochondrial DNA abnormality and mitochondrial dysfunction may be due to primary inflammation in MS or may be occurred itself before any inflammation, but definitely contributes to axonal degeneration and disease progression. Mitochondrial abnormality contributes to axonal degeneration in MS and disease progression.
1. Morató L, Bertini E, Verrigni D, Ardissone A, Ruiz M, Ferrer I, et al. Mitochondrial dysfunction in central nervous system white matter disorders. Glia 2014;62:1878-94.
2. Campbell GR, Worrall JT, Mahad DJ. The central role of mitochondria in axonal degeneration in multiple sclerosis. Mult Scler 2014;20:1806-13.
3. Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med 2014;20:179-87.
4. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12.
5. DiMauro S; Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003;348:2656-68.
6. Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med 2008;10:291-315.
7. Reddy PH. Mitochondrial oxidative damage in aging and Alzheimer’s disease: Implications for mitochondrially targeted antioxidant therapeutics. J Biomed Biotechnol 2006;3:31372.
8. Rajda C, Pukoli D, Bende Z, Majláth Z, Vécsei L. Excitotoxins, mitochondrial and redox disturbances in multiple sclerosis. Int J Mol Sci 2017;pii:E353.
9. Mancini A, Tantucci M, Mazzocchetti P, de Iure A, Durante V, Macchioni L. Microglial activation and the nitric oxide/cGMP/PKG pathway underlie enhanced neuronal vulnerability to mitochondrial dysfunction in experimental multiple sclerosis. Neurobiol Dis 2018;113:97-108.
10. Lan M, Tang X, Zhang J, Yao Z. Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes. Rev Neurosci 2018;29:39-53.
11. Kristofiková Z, Bocková M, Hegnerová K, Bartos A, Klaschka J, Rícný J, et al. Enhanced levels of mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis. Mol Biosyst 2009;50:1174-9.
12. Witte ME, Bø L, Rodenburg RJ, Belien JA, Musters R, Hazes T, et al. Enhanced number and activity of mitochondria in multiple sclerosis lesions. J Pathol 2009;219:193-204.
13. Witte ME, Geurts JJ, de Vries HE, van der Valk P, van Horssen J. Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion 2010;10: 411-8.
14. Mao PZ, Reddy PH. Is multiple sclerosis a mitochondrial disease? Biochim Biophys Acta 2010;1802:66-79.
15. Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A, Trapp BD, et al. Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol 2012;124:209-20.
16. Vyshkina T, Banisor I, Shugart YY, Leist TP, Kalman B, et al. Genetic variants of complex I in multiple sclerosis. J Neurol Sci 2005;228:55-64.
17. Vogler S, Goedde R, Miterski B, Gold R, Kroner A, Koczan D, et al. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. J Mol Med 2005;83:806-11.
18. Ban M, Elson J, Walton A, Turnbull D, Compston A, Chinnery P, et al. Investigation of the role of mitochondrial DNA in multiple sclerosis suscept- ibility. PLoS One 2008;3:e2891.
19. Yu X, Koczan D, Sulonen AM, Akkad DA, Kroner A, Comabella M, et al. mtDNA nt13708A variant increases the risk of multiple sclerosis. PLoS One 2008;3:e1530.
20. Harding AE, Sweeney MG, Miller DH, Mumford CJ, Kellar-Wood H, Menard D, et al. Compston, Occurrence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation. Brain 1992;115:979-89.
21. Andalib S, Talebi M, Sakhinia E, Farhoudi M, Sadeghi-Bazargani H, Emamhadi MR, et al. Mitochondrial DNA G13708A variation and multiple sclerosis: Is there an association? Rev Neurol 2017;173:164-8.
22. Mayr-Wohlfart U, Paulus C, Henneberg A, Rödel G. Mitochondrial DNA mutations in multiple sclerosis patients with severe optic involvement. Acta Neurol Scand 1996;94:167-71.
23. Hanefeld FA, Ernst BP, Wilichowski E, Christen HJ. Leber’s hereditary optic neuropathy mitochondrial DNA mutations in childhood multiple sclerosis. Neuropediatrics 1994;25:331.
24. Mihailova SM, Ivanova MI, Quin LM, Naumova EJ. Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis. Eur J Neurol 2007;14:44-7.
25. Andalib S, Talebi M, Sakhinia E, Farhoudi M, Sadeghi-Bazargani H. Mitochondrial DNA T4216C and A4917G variations in multiple sclerosis. J Neurol Sci 2015;356:55-60.
26. Penisson-Besnier I, Moreau C, Jacques C, Roger J, Dubas F, Reynier P. Multiple sclerosis and Leber's hereditary optic neuropathy mitochondrial DNA mutations. Rev Neurol 2001;157:537-41.
27. Chalmers RM, Robertson N, Compston DAS, Harding AE. Sequence of mitochondrial DNA in patients with multiple sclerosis. Ann Neurol 1996;40:239-43.
28. Vyshkina T, Sylvester A, Sadiq S, Bonilla E, Canter JA, Perl A, et al. Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus. Clin Immunol 2008;129:31-5.
29. Hwang JM, Chang BL, Park SS. Leber's hereditary optic neuropathy mutations in Korean patients with multiple sclerosis. Ophthalmologica 2001;215;398-400.
30. Nishimura M, Obayashi H, Ohta M, Uchiyama T, Hao Q, Saida T. No association of the 11778 mitochondrial DNA mutation and multiple sclerosis in Japan. Neurology 1995;45:1333-4.
31. Leuzzi V, Carducci C, Lanza M, Salvetti M, Ristori G, Giovanni S, et al. LHON mutations in Italian patients
affected by multiple sclerosis. Acta Neurol Scand 1997;96:145-8.
32. Kalman B, Lublin F, Alder H. Mitochondrial DNA mutations in multiple sclerosis. Mult Scler 1995;1:32-6.
33. Schoenfeld R, Wong A, Silva J, Li M, Itoh A, Horiuchi M, et al. Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation. Mitochondrion 2010;10:143-50.
34. Leurs CE, Podlesniy P, Trullas R, Balk L, Steenwijk MD, Malekzadeh A, et al. Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment. Mult Scler 2018;24:472-80.
35. Zambonin JL, Zhao C, Ohno N, Campbell GR, Engeham S, Ziabreva I, et al. Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis. Brain 2011;134:1901-13.
36. Dutta R, McDonough J, Yin X, Peterson J, Chang A, Torres T, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006;59:478-89.
37. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008;31:247-69.
38. Mahad D, Lassmann H, Turnbull D. Review: mitochondria and disease progression in multiple sclerosis. Neuropathol Appl Neurobiol 2008;34:577-89.
39. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-17.
40. Mahad DJ, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, et al. Mitochondrial changes within axons in multiple sclerosis. Brain 2009;132;1161-74.
41. Regenold WT, Phatak P, Makley MJ, Stone RD, Kling MA. Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression. J Neurol Sci 2008;275:106-12.
42. Kent-Braun JA, Ng AV, Castro M, Weiner MW, Gelinas D, Dudley GA, R.et al. Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis. J Appl Physiol 1997;83:1998-2004.
43. Bet L, Moggio M, Comi GP, Mariani C, Prelle A, Checcarelli N, et al. Multiple sclerosis and mitochondrial myopathy: an unusual combination of diseases. J Neurol 1994;241:511-6.
44. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005;434:658-62.
45. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al. Cyclophilin D-dependent mitochondrial perme-ability transition regulates some necrotic but not apoptotic cell death. Nature 2005;434:652-8.
46. Forte M, Gold BG, Marracci G, Chaudhary P, Basso E, Johnsen D, et al. Fowlkes, M. Rahder, K. Stem, P. Bernardi, D. Bourdette, Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc Natl Acad Sci U. S. A. 2007;104:7558-63.
47. Du H, Yan SS. Mitochondrial medicine for neurodegenerative diseases. Int J Biochem Cell Biol 2016;42:560-72.
48. Patergnani S, Fossati V, Bonora M, Giorgi C, Marchi S, Missiroli S, et al. Mitochondria in Multiple Sclerosis: Molecular Mechanisms of Pathogenesis. Int Rev Cell Mol Biol 2017;328:49-103.
49. Witte ME, Nijland PG, Drexhage JA, Gerritsen W, Geerts D, Van Het Hof B, et al. Reduced expression of PGC-1alpha partly underlies mitochondrial changes and correlates with neuronal loss in multiple sclerosis cortex. Acta Neuropathol 2013;125:231-43.
50. Pandit A, Vadnal J, Houston S, Freeman E, Mcdonough J. Impaired regulation of electron transport chain subunit genes by nuclear respiratory factor 2 in multiple sclerosis. J Neurol Sci 2009;279:14-20.
51. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004;18:357-68.
52. Cassina AM; Hodara R; Souza JM; Thomson L; Castro L, Ischiropoulos H, et al. Cytochrome C nitration by peroxynitrite. J Biol Chem 2000;275:21409-15.
53. Brown GC; Borutaite V. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta 2004;1658:44-9.
54. Yamamoto T, Maruyama W, Kato Y, Yi H, Shamoto-Nagai M, Tanaka M, et al. Selective nitration of mitochondrial complex I by peroxynitrite: Involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cells. J Neural Transm 2002;109:1-13.
55. Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J. Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J Biol Chem 2006;281:31950-62.
56. Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction: Demyelinated axons are especially susceptible. Brain 1997;120:2149-57.
57. Shrager P, Custer AW, Kazarinova K, Rasband MN, Mattson D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J Neurophysiol 1998;79:529-36.
58. Sadeghian M, Mastrolia V, Rezaei Haddad A, Mosley A, Mullali G, Schiza D, et al. Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis. Sci Rep 2016;6:33249.
59. Haile Y, Deng X, Ortiz-Sandoval C, Tahbaz N, Janowicz A, Lu JQ, et al. Rab32 connects ER stress to mitochondrial defects in multiple sclerosis. J Neuroinflammation 2017;14:19.
60. Di Filippo M, Tozzi A, Tantucci M, Arcangeli S, Chiasserini D, Ghiglieri V, et al. Interferon-β1a protects neurons against mitochondrial toxicity via modulation of STAT1 signaling: Electrophysiological evidence. Neurobiol Dis 2014;62:387-93.
2. Campbell GR, Worrall JT, Mahad DJ. The central role of mitochondria in axonal degeneration in multiple sclerosis. Mult Scler 2014;20:1806-13.
3. Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med 2014;20:179-87.
4. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12.
5. DiMauro S; Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003;348:2656-68.
6. Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med 2008;10:291-315.
7. Reddy PH. Mitochondrial oxidative damage in aging and Alzheimer’s disease: Implications for mitochondrially targeted antioxidant therapeutics. J Biomed Biotechnol 2006;3:31372.
8. Rajda C, Pukoli D, Bende Z, Majláth Z, Vécsei L. Excitotoxins, mitochondrial and redox disturbances in multiple sclerosis. Int J Mol Sci 2017;pii:E353.
9. Mancini A, Tantucci M, Mazzocchetti P, de Iure A, Durante V, Macchioni L. Microglial activation and the nitric oxide/cGMP/PKG pathway underlie enhanced neuronal vulnerability to mitochondrial dysfunction in experimental multiple sclerosis. Neurobiol Dis 2018;113:97-108.
10. Lan M, Tang X, Zhang J, Yao Z. Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes. Rev Neurosci 2018;29:39-53.
11. Kristofiková Z, Bocková M, Hegnerová K, Bartos A, Klaschka J, Rícný J, et al. Enhanced levels of mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis. Mol Biosyst 2009;50:1174-9.
12. Witte ME, Bø L, Rodenburg RJ, Belien JA, Musters R, Hazes T, et al. Enhanced number and activity of mitochondria in multiple sclerosis lesions. J Pathol 2009;219:193-204.
13. Witte ME, Geurts JJ, de Vries HE, van der Valk P, van Horssen J. Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion 2010;10: 411-8.
14. Mao PZ, Reddy PH. Is multiple sclerosis a mitochondrial disease? Biochim Biophys Acta 2010;1802:66-79.
15. Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A, Trapp BD, et al. Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol 2012;124:209-20.
16. Vyshkina T, Banisor I, Shugart YY, Leist TP, Kalman B, et al. Genetic variants of complex I in multiple sclerosis. J Neurol Sci 2005;228:55-64.
17. Vogler S, Goedde R, Miterski B, Gold R, Kroner A, Koczan D, et al. Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis. J Mol Med 2005;83:806-11.
18. Ban M, Elson J, Walton A, Turnbull D, Compston A, Chinnery P, et al. Investigation of the role of mitochondrial DNA in multiple sclerosis suscept- ibility. PLoS One 2008;3:e2891.
19. Yu X, Koczan D, Sulonen AM, Akkad DA, Kroner A, Comabella M, et al. mtDNA nt13708A variant increases the risk of multiple sclerosis. PLoS One 2008;3:e1530.
20. Harding AE, Sweeney MG, Miller DH, Mumford CJ, Kellar-Wood H, Menard D, et al. Compston, Occurrence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation. Brain 1992;115:979-89.
21. Andalib S, Talebi M, Sakhinia E, Farhoudi M, Sadeghi-Bazargani H, Emamhadi MR, et al. Mitochondrial DNA G13708A variation and multiple sclerosis: Is there an association? Rev Neurol 2017;173:164-8.
22. Mayr-Wohlfart U, Paulus C, Henneberg A, Rödel G. Mitochondrial DNA mutations in multiple sclerosis patients with severe optic involvement. Acta Neurol Scand 1996;94:167-71.
23. Hanefeld FA, Ernst BP, Wilichowski E, Christen HJ. Leber’s hereditary optic neuropathy mitochondrial DNA mutations in childhood multiple sclerosis. Neuropediatrics 1994;25:331.
24. Mihailova SM, Ivanova MI, Quin LM, Naumova EJ. Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis. Eur J Neurol 2007;14:44-7.
25. Andalib S, Talebi M, Sakhinia E, Farhoudi M, Sadeghi-Bazargani H. Mitochondrial DNA T4216C and A4917G variations in multiple sclerosis. J Neurol Sci 2015;356:55-60.
26. Penisson-Besnier I, Moreau C, Jacques C, Roger J, Dubas F, Reynier P. Multiple sclerosis and Leber's hereditary optic neuropathy mitochondrial DNA mutations. Rev Neurol 2001;157:537-41.
27. Chalmers RM, Robertson N, Compston DAS, Harding AE. Sequence of mitochondrial DNA in patients with multiple sclerosis. Ann Neurol 1996;40:239-43.
28. Vyshkina T, Sylvester A, Sadiq S, Bonilla E, Canter JA, Perl A, et al. Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus. Clin Immunol 2008;129:31-5.
29. Hwang JM, Chang BL, Park SS. Leber's hereditary optic neuropathy mutations in Korean patients with multiple sclerosis. Ophthalmologica 2001;215;398-400.
30. Nishimura M, Obayashi H, Ohta M, Uchiyama T, Hao Q, Saida T. No association of the 11778 mitochondrial DNA mutation and multiple sclerosis in Japan. Neurology 1995;45:1333-4.
31. Leuzzi V, Carducci C, Lanza M, Salvetti M, Ristori G, Giovanni S, et al. LHON mutations in Italian patients
affected by multiple sclerosis. Acta Neurol Scand 1997;96:145-8.
32. Kalman B, Lublin F, Alder H. Mitochondrial DNA mutations in multiple sclerosis. Mult Scler 1995;1:32-6.
33. Schoenfeld R, Wong A, Silva J, Li M, Itoh A, Horiuchi M, et al. Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation. Mitochondrion 2010;10:143-50.
34. Leurs CE, Podlesniy P, Trullas R, Balk L, Steenwijk MD, Malekzadeh A, et al. Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment. Mult Scler 2018;24:472-80.
35. Zambonin JL, Zhao C, Ohno N, Campbell GR, Engeham S, Ziabreva I, et al. Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis. Brain 2011;134:1901-13.
36. Dutta R, McDonough J, Yin X, Peterson J, Chang A, Torres T, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006;59:478-89.
37. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008;31:247-69.
38. Mahad D, Lassmann H, Turnbull D. Review: mitochondria and disease progression in multiple sclerosis. Neuropathol Appl Neurobiol 2008;34:577-89.
39. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-17.
40. Mahad DJ, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, et al. Mitochondrial changes within axons in multiple sclerosis. Brain 2009;132;1161-74.
41. Regenold WT, Phatak P, Makley MJ, Stone RD, Kling MA. Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression. J Neurol Sci 2008;275:106-12.
42. Kent-Braun JA, Ng AV, Castro M, Weiner MW, Gelinas D, Dudley GA, R.et al. Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis. J Appl Physiol 1997;83:1998-2004.
43. Bet L, Moggio M, Comi GP, Mariani C, Prelle A, Checcarelli N, et al. Multiple sclerosis and mitochondrial myopathy: an unusual combination of diseases. J Neurol 1994;241:511-6.
44. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005;434:658-62.
45. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al. Cyclophilin D-dependent mitochondrial perme-ability transition regulates some necrotic but not apoptotic cell death. Nature 2005;434:652-8.
46. Forte M, Gold BG, Marracci G, Chaudhary P, Basso E, Johnsen D, et al. Fowlkes, M. Rahder, K. Stem, P. Bernardi, D. Bourdette, Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc Natl Acad Sci U. S. A. 2007;104:7558-63.
47. Du H, Yan SS. Mitochondrial medicine for neurodegenerative diseases. Int J Biochem Cell Biol 2016;42:560-72.
48. Patergnani S, Fossati V, Bonora M, Giorgi C, Marchi S, Missiroli S, et al. Mitochondria in Multiple Sclerosis: Molecular Mechanisms of Pathogenesis. Int Rev Cell Mol Biol 2017;328:49-103.
49. Witte ME, Nijland PG, Drexhage JA, Gerritsen W, Geerts D, Van Het Hof B, et al. Reduced expression of PGC-1alpha partly underlies mitochondrial changes and correlates with neuronal loss in multiple sclerosis cortex. Acta Neuropathol 2013;125:231-43.
50. Pandit A, Vadnal J, Houston S, Freeman E, Mcdonough J. Impaired regulation of electron transport chain subunit genes by nuclear respiratory factor 2 in multiple sclerosis. J Neurol Sci 2009;279:14-20.
51. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004;18:357-68.
52. Cassina AM; Hodara R; Souza JM; Thomson L; Castro L, Ischiropoulos H, et al. Cytochrome C nitration by peroxynitrite. J Biol Chem 2000;275:21409-15.
53. Brown GC; Borutaite V. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta 2004;1658:44-9.
54. Yamamoto T, Maruyama W, Kato Y, Yi H, Shamoto-Nagai M, Tanaka M, et al. Selective nitration of mitochondrial complex I by peroxynitrite: Involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cells. J Neural Transm 2002;109:1-13.
55. Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J. Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J Biol Chem 2006;281:31950-62.
56. Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction: Demyelinated axons are especially susceptible. Brain 1997;120:2149-57.
57. Shrager P, Custer AW, Kazarinova K, Rasband MN, Mattson D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J Neurophysiol 1998;79:529-36.
58. Sadeghian M, Mastrolia V, Rezaei Haddad A, Mosley A, Mullali G, Schiza D, et al. Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis. Sci Rep 2016;6:33249.
59. Haile Y, Deng X, Ortiz-Sandoval C, Tahbaz N, Janowicz A, Lu JQ, et al. Rab32 connects ER stress to mitochondrial defects in multiple sclerosis. J Neuroinflammation 2017;14:19.
60. Di Filippo M, Tozzi A, Tantucci M, Arcangeli S, Chiasserini D, Ghiglieri V, et al. Interferon-β1a protects neurons against mitochondrial toxicity via modulation of STAT1 signaling: Electrophysiological evidence. Neurobiol Dis 2014;62:387-93.
| Files | ||
| Issue | Vol 57, No 1 (2019) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/acta.v57i1.1748 | |
| Keywords | ||
| Multiple sclerosis Disease progression DNA Mitochondria | ||
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How to Cite
1.
Saberi A, Kazemi S. Mitochondrial Dysfunction in Multiple Sclerosis: A Systematic Review. Acta Med Iran. 2019;57(1):5-16.
