Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias

Author(s): Emanuele Barca*, Valentina Emmanuele, Salvatore DiMauro, Antonio Toscano and Catarina M. Quinzii

Volume 17, Issue 1, 2019

Page: [21 - 32] Pages: 12

DOI: 10.2174/1570159X15666171109125643

Price: $65

conference banner
Abstract

Background: Hereditary cerebellar ataxias are a group of disorders characterized by heterogeneous clinical manifestations, progressive clinical course, and diverse genetic causes. No disease modifying treatments are yet available for many of these disorders. Oxidative stress has been recurrently identified in different progressive cerebellar diseases, and it represents a widely investigated target for treatment.

Objective: To review the main aspects and new perspectives of antioxidant therapy in cerebellar ataxias ranging from bench to bedside.

Method: This article is a summary of the state-of-the-art on the use of antioxidant molecules in cerebellar ataxia treatments. It also briefly summarizes aspects of oxidative stress production and general characteristics of antioxidant compounds.

Results: Antioxidants represent a vast category of compounds; old drugs have been extensively studied and modified in order to achieve better biological effects. Despite the vast body of literature present on the use of antioxidants in cerebellar ataxias, for the majority of these disorders conclusive results on the efficacy are still missing.

Conclusion: Antioxidant therapy in cerebellar ataxias is a promising field of investigations. To achieve the success in identifying the correct treatment more work needs to be done. In particular, a combined effort is needed by basic scientists in developing more efficient molecules, and by clinical researchers together with patients communities, to run clinical trials in order to identify conclusive treatments strategies.

Keywords: Antioxidants, cerebellar ataxia, coenzyme Q10, idebenone, ataxias, oxidative stress.

« Previous Next »
Graphical Abstract

[1]
Bodranghien, F.; Bastian, A.; Casali, C.; Hallett, M.; Louis, E.D.; Manto, M.; Mariën, P.; Nowak, D.A.; Schmahmann, J.D.; Serrao, M.; Steiner, K.M.; Strupp, M.; Tilikete, C.; Timmann, D.; van Dun, K. Consensus paper: Revisiting the symptoms and signs of cerebellar syndrome. Cerebellum, 2016, 15(3), 369-391. [http://dx.doi. org/10.1007/s12311-015-0687-3]. [PMID: 26105056].
[2]
Manto, M.; Haines, D. Cerebellar research: two centuries of discoveries. Cerebellum, 2012, 11(2), 446-448. [http://dx.doi.org/10. 1007/s12311-011-0336-4]. [PMID: 22113501].
[3]
Manto, M. The cerebellum, cerebellar disorders, and cerebellar research--two centuries of discoveries. Cerebellum, 2008, 7(4), 505-516. [http://dx.doi.org/10.1007/s12311-008-0063-7]. [PMID: 18855093].
[4]
Ilg, W.; Bastian, A.J.; Boesch, S.; Burciu, R.G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.; Timmann, D. Consensus paper: Management of degenerative cerebellar disorders. Cerebellum, 2014, 13(2), 248-268. [http://dx.doi.org/10.1007/s12311-013-0531-6]. [PMID: 24222635].
[5]
Giannoccaro, M.P.; La Morgia, C.; Rizzo, G.; Carelli, V. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson’s disease. Mov. Disord., 2017, 32(3), 346-363. [http://dx.doi. org/10.1002/mds.26966]. [PMID: 28251677].
[6]
Islam, M.T. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol. Res., 2017, 39(1), 73-82. [http:// dx.doi.org/10.1080/01616412.2016.1251711]. [PMID: 27809706].
[7]
Zeviani, M.; Simonati, A.; Bindoff, L.A. Ataxia in mitochondrial disorders. Handb. Clin. Neurol., 2012, 103, 359-372. [http:// dx.doi.org/10.1016/B978-0-444-51892-7.00022-X]. [PMID: 21827900].
[8]
Miller, D.M.; Buettner, G.R.; Aust, S.D. Transition metals as catalysts of “autoxidation” reactions. Free Radic. Biol. Med., 1990, 8(1), 95-108. [http://dx.doi.org/10.1016/0891-5849(90)90148-C]. [PMID: 2182396].
[9]
Pastor, N.; Weinstein, H.; Jamison, E.; Brenowitz, M. A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in the mechanism of sequence-specific binding. J. Mol. Biol., 2000, 304(1), 55-68. [http://dx.doi.org/10. 1006/jmbi.2000.4173]. [PMID: 11071810].
[10]
DiMauro, S.; Schon, E.A.; Carelli, V.; Hirano, M. The clinical maze of mitochondrial neurology. Nat. Rev. Neurol., 2013, 9(8), 429-444. [http://dx.doi.org/10.1038/nrneurol.2013.126]. [PMID: 23835535].
[11]
Indo, H.P.; Yen, H.C.; Nakanishi, I.; Matsumoto, K.; Tamura, M.; Nagano, Y.; Matsui, H.; Gusev, O.; Cornette, R.; Okuda, T.; Minamiyama, Y.; Ichikawa, H.; Suenaga, S.; Oki, M.; Sato, T.; Ozawa, T.; Clair, D.K.; Majima, H.J. A mitochondrial superoxide theory for oxidative stress diseases and aging. J. Clin. Biochem. Nutr., 2015, 56(1), 1-7. [http://dx.doi.org/10.3164/jcbn.14-42]. [PMID: 25834301].
[12]
Indo, H.P. Hawkins, C. L.; Nakanishi, I.; Matsumoto, K. I.; Matsui, H.; Suenaga, S.; Davies, M. J.; St Clair, D. K.; Ozawa, T.; Majima, H. J. Role of mitochondrial reactive oxygen species in the activation of cellular signals, Molecules, and Function. Handb. Exp. Pharmacol., 2017, 240, 439-456.
[13]
Finkel, T.; Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature, 2000, 408(6809), 239-247. [http://dx. doi.org/10.1038/35041687]. [PMID: 11089981].
[14]
Petrat, F.; de Groot, H.; Rauen, U. Subcellular distribution of chelatable iron: a laser scanning microscopic study in isolated hepatocytes and liver endothelial cells. Biochem. J., 2001, 356(Pt 1), 61-69. [http://dx.doi.org/10.1042/bj3560061]. [PMID: 11336636].
[15]
Kakhlon, O.; Cabantchik, Z.I. The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic. Biol. Med., 2002, 33(8), 1037-1046. [http://dx.doi.org/10. 1016/S0891-5849(02)01006-7]. [PMID: 12374615].
[16]
De Grey, A.D. HO2*: the forgotten radical. DNA Cell Biol., 2002, 21(4), 251-257. [http://dx.doi.org/10.1089/104454902753759672]. [PMID: 12042065].
[17]
Bhatti, J.S.; Bhatti, G.K.; Reddy, P.H. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim. Biophys. Acta Mol. Basis Dis, 2017, 1863(5), 1066-1077. [http://dx.doi.org/10.1016/ j.bbadis.2016.11.010]. [PMID: 27836629].
[18]
Ridnour, L.A.; Thomas, D.D.; Mancardi, D.; Espey, M.G.; Miranda, K.M.; Paolocci, N.; Feelisch, M.; Fukuto, J.; Wink, D.A. The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. Biol. Chem., 2004, 385(1), 1-10. [http://dx.doi. org/10.1515/BC.2004.001]. [PMID: 14977040].
[19]
Jones, D.P. Redefining oxidative stress. Antioxid. Redox Signal., 2006, 8(9-10), 1865-1879. [http://dx.doi.org/10.1089/ars.2006.8.1865]. [PMID: 16987039].
[20]
Bhagavan, H.N.; Chopra, R.K. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res., 2006, 40(5), 445-453. [http://dx.doi.org/10.1080/10715760600617843]. [PMID: 16551570].
[21]
Matthews, R.T.; Yang, L.; Browne, S.; Baik, M.; Beal, M.F. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc. Natl. Acad. Sci. USA, 1998, 95(15), 8892-8897. [http://dx.doi.org/10.1073/pnas.95. 15.8892]. [PMID: 9671775].
[22]
Beyer, R.E. An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem. Cell Biol., 1992, 70(6), 390-403. [http://dx.doi.org/10.1139/o92-061]. [PMID: 1333230].
[23]
Ernster, L.; Dallner, G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta, 1995, 1271(1), 195-204. [http://dx.doi.org/10.1016/0925-4439(95)00028-3]. [PMID: 7599208].
[24]
Quinzii, C.M.; Emmanuele, V.; Hirano, M. Clinical presentations of coenzyme q10 deficiency syndrome. Mol. Syndromol., 2014, 5(3-4), 141-146. [http://dx.doi.org/10.1159/000360490]. [PMID: 25126046].
[25]
Balreira, A.; Boczonadi, V.; Barca, E.; Pyle, A.; Bansagi, B.; Appleton, M.; Graham, C.; Hargreaves, I.P.; Rasic, V.M.; Lochmüller, H.; Griffin, H.; Taylor, R.W.; Naini, A.; Chinnery, P.F.; Hirano, M.; Quinzii, C.M.; Horvath, R. ANO10 mutations cause ataxia and coenzyme Q10 deficiency. J. Neurol., 2014, 261(11), 2192-2198. [http://dx.doi.org/10.1007/s00415-014-7476-7]. [PMID: 25182700].
[26]
Quinzii, C.M.; Kattah, A.G.; Naini, A.; Akman, H.O.; Mootha, V.K.; DiMauro, S.; Hirano, M. Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology, 2005, 64(3), 539-541. [http://dx.doi.org/10.1212/01.WNL.0000150588. 75281.58]. [PMID: 15699391].
[27]
Barca, E.; Kleiner, G.; Tang, G.; Ziosi, M.; Tadesse, S.; Masliah, E.; Louis, E.D.; Faust, P.; Kang, U.J.; Torres, J.; Cortes, E.P.; Vonsattel, J.P.; Kuo, S.H.; Quinzii, C.M. Decreased coenzyme Q10 levels in multiple system atrophy cerebellum. J. Neuropathol. Exp. Neurol., 2016, 75(7), 663-672. [http://dx.doi.org/10.1093/ jnen/nlw037]. [PMID: 27235405].
[28]
Schottlaender, L.V.; Bettencourt, C.; Kiely, A.P.; Chalasani, A.; Neergheen, V.; Holton, J.L.; Hargreaves, I.; Houlden, H. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients. PLoS One, 2016, 11(2), e0149557. [http://dx.doi.org/10.1371/journal.pone.0149557]. [PMID: 26894433].
[29]
C. I. Hyson, H. C.; Kieburtz, K.; Shoulson, I.; McDermott, M.; Ravina, B.; de Blieck, E. A.; Cudkowicz, M. E.; Ferrante, R. J.; Como, P.; Frank, S.; Zim-merman, C.; Cudkowicz, M. E.; Ferrante, K.; Newhall, K.; Jennings, D.; Kelsey, T.; Walker, F.; Hunt, V.; Daigneault, S.; Goldstein, M.; Weber, J.; Watts, A.; Beal, M. F.; Browne, S. E.; Metakis, L. J., Safety and tolerability of high-dosage coen-zyme Q10 in Huntington’s disease and healthy subjects. Mov. Disord., 2010, 25(12), 1924-1928. [PMID: 20669312].
[30]
Emmanuele, V.; López, L.C.; Berardo, A.; Naini, A.; Tadesse, S.; Wen, B.; D’Agostino, E.; Solomon, M.; DiMauro, S.; Quinzii, C.; Hirano, M. Heterogeneity of coenzyme Q10 deficiency: patient study and literature review. Arch. Neurol., 2012, 69(8), 978-983. [http://dx.doi.org/10.1001/archneurol.2012.206]. [PMID: 22490322].
[31]
Matsuda, Y.; Masahara, R. Photostability of solid-state ubidecarenone at ordinary and elevated temperatures under exaggerated UV irradiation. J. Pharm. Sci., 1983, 72(10), 1198-1203. [http://dx.doi.org/10.1002/jps.2600721023]. [PMID: 6644572].
[32]
López, L.C.; Quinzii, C.M.; Area, E.; Naini, A.; Rahman, S.; Schuelke, M.; Salviati, L.; Dimauro, S.; Hirano, M. Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects. PLoS One, 2010, 5(7), e11897. [http://dx.doi.org/10.1371/journal.pone.0011897]. [PMID: 20689595].
[33]
Suno, M.; Nagaoka, A. Inhibition of lipid peroxidation by a novel compound, idebenone (CV-2619). Jpn. J. Pharmacol., 1984, 35(2), 196-198. [http://dx.doi.org/10.1254/jjp.35.196]. [PMID: 6748380].
[34]
Geromel, V.; Darin, N.; Chrétien, D.; Bénit, P.; DeLonlay, P.; Rötig, A.; Munnich, A.; Rustin, P.; Coenzyme, Q. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol. Genet. Metab., 2002, 77(1-2), 21-30. [http://dx.doi.org/10.1016/S1096-7192(02)00145-2]. [PMID: 12359126].
[35]
Mordente, A.; Martorana, G.E.; Minotti, G.; Giardina, B. Antioxidant properties of 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (idebenone). Chem. Res. Toxicol., 1998, 11(1), 54-63. [http://dx.doi.org/10.1021/tx970136j]. [PMID: 9477226].
[36]
Kutz, K.; Drewe, J.; Vankan, P. Pharmacokinetic properties and metabolism of idebenone. J. Neurol., 2009, 256(Suppl. 1), 31-35. [http://dx.doi.org/10.1007/s00415-009-1006-z]. [PMID: 19283348].
[37]
Jaber, S.; Polster, B.M. Idebenone and neuroprotection: antioxidant, pro-oxidant, or electron carrier? J. Bioenerg. Biomembr., 2015, 47(1-2), 111-118. [http://dx.doi.org/10.1007/s10863-014-9571-y]. [PMID: 25262284].
[38]
Yu-Wai-Man, P.; Soiferman, D.; Moore, D.G.; Burté, F.; Saada, A. Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy. Mitochondrion, 2017, 36, 36-42. [http://dx.doi.org/10.1016/j.mito.2017.01. 004]. [PMID: 28093355].
[39]
Klopstock, T.; Metz, G.; Yu-Wai-Man, P.; Büchner, B.; Gallenmüller, C.; Bailie, M.; Nwali, N.; Griffiths, P.G.; von Livonius, B.; Reznicek, L.; Rouleau, J.; Coppard, N.; Meier, T.; Chinnery, P.F. Persistence of the treatment effect of idebenone in Leber’s hereditary optic neuropathy. Brain, 2013, 136(Pt 2), e230. [http://dx.doi. org/10.1093/brain/aws279]. [PMID: 23388409].
[40]
Carelli, V.; La Morgia, C.; Valentino, M.L.; Rizzo, G.; Carbonelli, M.; De Negri, A.M.; Sadun, F.; Carta, A.; Guerriero, S.; Simonelli, F.; Sadun, A.A.; Aggarwal, D.; Liguori, R.; Avoni, P.; Baruzzi, A.; Zeviani, M.; Montagna, P.; Barboni, P. Idebenone treatment in Leber’s hereditary optic neuropathy. Brain, 2011, 134(Pt 9), e188. [http://dx.doi.org/10.1093/brain/awr180]. [PMID: 21810891].
[41]
Imada, I.; Fujita, T.; Sugiyama, Y.; Okamoto, K.; Kobayashi, Y. Effects of idebenone and related compounds on respiratory activities of brain mitochondria, and on lipid peroxidation of their membranes. Arch. Gerontol. Geriatr., 1989, 8(3), 323-341. [http://dx. doi.org/10.1016/0167-4943(89)90014-9]. [PMID: 2764646].
[42]
Brière, J.J.; Schlemmer, D.; Chretien, D.; Rustin, P. Quinone analogues regulate mitochondrial substrate competitive oxidation. Biochem. Biophys. Res. Commun., 2004, 316(4), 1138-1142. [http://dx. doi.org/10.1016/j.bbrc.2004.03.002]. [PMID: 15044103].
[43]
Dinkova-Kostova, A.T.; Talalay, P. NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch. Biochem. Biophys., 2010, 501(1), 116-123. [http://dx.doi.org/10.1016/j.abb.2010.03. 019]. [PMID: 20361926].
[44]
Niki, E. Tocopherylquinone and tocopherylhydroquinone. Redox Rep., 2007, 12(5), 204-210. [http://dx.doi.org/10.1179/135100007X 200353]. [PMID: 17925092].
[45]
Hughes, P.E.; Tove, S.B. Synthesis of alpha-tocopherolquinone by the rat and its reduction by mitochondria. J. Biol. Chem., 1980, 255(15), 7095-7097. [PMID: 7391070].
[46]
Hawi, A.; Heald, S.; Sciascia, T. Use of an adaptive study design in single ascending-dose pharmacokinetics of A0001 (α-tocopherylquinone) in healthy male subjects. J. Clin. Pharmacol., 2012, 52(1), 65-77. [http://dx.doi.org/10.1177/0091270010390807]. [PMID: 21343342].
[47]
Lynch, D.R.; Willi, S.M.; Wilson, R.B.; Cotticelli, M.G.; Brigatti, K.W.; Deutsch, E.C.; Kucheruk, O.; Shrader, W.; Rioux, P.; Miller, G.; Hawi, A.; Sciascia, T. A0001 in Friedreich ataxia: biochemical characterization and effects in a clinical trial. Mov. Disord., 2012, 27(8), 1026-1033. [http://dx.doi.org/10.1002/mds.25058]. [PMID: 22744651].
[48]
Bidichandani, S.I.; Delatycki, M.B. Friedreich Ataxia.In GeneReviews( R)Seattle (WA), 1993, 2018.
[49]
Shrader, W.D.; Amagata, A.; Barnes, A.; Enns, G.M.; Hinman, A.; Jankowski, O.; Kheifets, V.; Komatsuzaki, R.; Lee, E.; Mollard, P.; Murase, K.; Sadun, A.A.; Thoolen, M.; Wesson, K.; Miller, G. α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorg. Med. Chem. Lett., 2011, 21(12), 3693-3698. [http://dx.doi.org/10.1016/j.bmcl.2011.04.085]. [PMID: 21600768].
[50]
Enns, G.M. Treatment of mitochondrial disorders: antioxidants and beyond. J. Child Neurol., 2014, 29(9), 1235-1240. [http://dx.doi. org/10.1177/0883073814538509]. [PMID: 24985754].
[51]
Enns, G.M.; Kinsman, S.L.; Perlman, S.L.; Spicer, K.M.; Abdenur, J.E.; Cohen, B.H.; Amagata, A.; Barnes, A.; Kheifets, V.; Shrader, W.D.; Thoolen, M.; Blankenberg, F.; Miller, G. Initial experience in the treatment of inherited mitochondrial disease with EPI-743. Mol. Genet. Metab., 2012, 105(1), 91-102. [http://dx.doi.org/10. 1016/j.ymgme.2011.10.009]. [PMID: 22115768].
[52]
Murphy, M.P.; Smith, R.A. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 629-656. [http://dx.doi.org/10.1146/annurev.pharmtox. 47.120505.105110]. [PMID: 17014364].
[53]
Ross, M.F.; Kelso, G.F.; Blaikie, F.H.; James, A.M.; Cochemé, H.M.; Filipovska, A.; Da Ros, T.; Hurd, T.R.; Smith, R.A.; Murphy, M.P. Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry (Mosc.), 2005, 70(2), 222-230. [http://dx.doi.org/10.1007/s10541-005-0104-5]. [PMID: 15807662].
[54]
Murphy, M.P. Understanding and preventing mitochondrial oxidative damage. Biochem. Soc. Trans., 2016, 44(5), 1219-1226. [http://dx.doi.org/10.1042/BST20160108]. [PMID: 27911703].
[55]
Kelso, G.F.; Porteous, C.M.; Coulter, C.V.; Hughes, G.; Porteous, W.K.; Ledgerwood, E.C.; Smith, R.A.; Murphy, M.P. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J. Biol. Chem., 2001, 276(7), 4588-4596. [http://dx.doi.org/10.1074/jbc.M009093200]. [PMID: 11092892].
[56]
James, A.M.; Sharpley, M.S.; Manas, A.R.; Frerman, F.E.; Hirst, J.; Smith, R.A.; Murphy, M.P. Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases. J. Biol. Chem., 2007, 282(20), 14708-14718. [http://dx.doi.org/10.1074/jbc.M611463200]. [PMID: 17369262].
[57]
Asin-Cayuela, J.; Manas, A.R.; James, A.M.; Smith, R.A.; Murphy, M.P. Fine-tuning the hydrophobicity of a mitochondria-targeted antioxidant. FEBS Lett., 2004, 571(1-3), 9-16. [http://dx.doi.org/10. 1016/j.febslet.2004.06.045]. [PMID: 15280009].
[58]
Snow, B.J.; Rolfe, F.L.; Lockhart, M.M.; Frampton, C.M.; O’Sullivan, J.D.; Fung, V.; Smith, R.A.; Murphy, M.P.; Taylor, K.M. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson’s disease. Mov. Disord., 2010, 25(11), 1670-1674. [http://dx.doi.org/10.1002/mds.23148]. [PMID: 20568096].
[59]
Wagner, K.H.; Kamal-Eldin, A.; Elmadfa, I. Gamma-tocopherol--an underestimated vitamin? Ann. Nutr. Metab., 2004, 48(3), 169-188. [http://dx.doi.org/10.1159/000079555]. [PMID: 15256801].
[60]
Muller, D.P.; Harries, J.T.; Lloyd, J.K. The relative importance of the factors involved in the absorption of vitamin E in children. Gut, 1974, 15(12), 966-971. [http://dx.doi.org/10.1136/gut.15.12.966]. [PMID: 4448411].
[61]
Baydas, G.; Karatas, F.; Gursu, M.F.; Bozkurt, H.A.; Ilhan, N.; Yasar, A.; Canatan, H. Antioxidant vitamin levels in term and preterm infants and their relation to maternal vitamin status. Arch. Med. Res., 2002, 33(3), 276-280. [http://dx.doi.org/10.1016/S0188-4409(02)00356-9]. [PMID: 12031634].
[62]
Ulatowski, L.; Parker, R.; Warrier, G.; Sultana, R.; Butterfield, D.A.; Manor, D. Vitamin E is essential for Purkinje neuron integrity. Neuroscience, 2014, 260, 120-129. [http://dx.doi.org/10.1016/ j.neuroscience.2013.12.001]. [PMID: 24342566].
[63]
Cavalier, L.; Ouahchi, K.; Kayden, H.J.; Di Donato, S.; Reutenauer, L.; Mandel, J.L.; Koenig, M. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am. J. Hum. Genet., 1998, 62(2), 301-310. [http://dx.doi.org/10.1086/301699]. [PMID: 9463307].
[64]
Mardones, P.; Rigotti, A. Cellular mechanisms of vitamin E uptake: relevance in alpha-tocopherol metabolism and potential implications for disease. J. Nutr. Biochem., 2004, 15(5), 252-260. [http://dx.doi.org/10.1016/j.jnutbio.2004.02.006]. [PMID: 15135148].
[65]
Borel, P.; Preveraud, D.; Desmarchelier, C. Bioavailability of vitamin E in humans: an update. Nutr. Rev., 2013, 71(6), 319-331. [http://dx.doi.org/10.1111/nure.12026]. [PMID: 23731443].
[66]
Muller, D.P.; Lloyd, J.K.; Wolff, O.H. Vitamin E and neurological function. Lancet, 1983, 1(8318), 225-228. [http://dx.doi.org/10. 1016/S0140-6736(83)92598-9]. [PMID: 6130255].
[67]
Muller, D.P. Vitamin E and neurological function. Mol. Nutr. Food Res., 2010, 54(5), 710-718. [http://dx.doi.org/10.1002/mnfr. 200900460]. [PMID: 20183831].
[68]
Nishimura, Y.; Hara, H. Integrated approaches to drug discovery for oxidative stress-related retinal diseases. Oxid. Med. Cell. Longev., 2016, 2016, 2370252. [http://dx.doi.org/10.1155/2016/ 2370252]. [PMID: 28053689].
[69]
Wang, H.; O’Reilly, E.J.; Weisskopf, M.G.; Logroscino, G.; McCullough, M.L.; Schatzkin, A.; Kolonel, L.N.; Ascherio, A. Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. Am. J. Epidemiol., 2011, 173(6), 595-602. [http://dx.doi.org/10.1093/aje/kwq416]. [PMID: 21335424].
[70]
Schuelke, M. Ataxia with Vitamin E Deficiency. In GeneReviews( R)Seattle (WA), 2016
[71]
Loughrill, E.; Govinden, P.; Zand, N. Vitamins A and E content of commercial infant foods in the UK: A cause for concern? Food Chem., 2016, 210, 56-62. [http://dx.doi.org/10.1016/j.foodchem. 2016.04.014]. [PMID: 27211620].
[72]
Bahtouee, M.; Monavarsadegh, G.; Ahmadipour, M.; Motieilangroodi, M.; Motamed, N.; Saberifard, J.; Eghbali, S.; Adibi, H.; Maneshi, H.; Malekizadeh, H. Acetylcysteine in the treatment of subacute sinusitis: A double-blind placebo-controlled clinical trial. Ear Nose Throat J., 2017, 96(1), E7-E11. [PMID: 28122105].
[73]
Yoon, E.; Babar, A.; Choudhary, M.; Kutner, M.; Pyrsopoulos, N. Acetaminophen-induced hepatotoxicity: A comprehensive update. J. Clin. Transl. Hepatol., 2016, 4(2), 131-142. [PMID: 27350943].
[74]
Bavarsad Shahripour, R.; Harrigan, M.R.; Alexandrov, A.V. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav., 2014, 4(2), 108-122. [http://dx.doi.org/10.1002/brb3.208]. [PMID: 24683506].
[75]
Huang, C.S.; He, W.; Meister, A.; Anderson, M.E. Amino acid sequence of rat kidney glutathione synthetase. Proc. Natl. Acad. Sci. USA, 1995, 92(4), 1232-1236. [http://dx.doi.org/10.1073/pnas. 92.4.1232]. [PMID: 7862666].
[76]
Arakawa, M.; Ito, Y. N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. Cerebellum, 2007, 6(4), 308-314. [http://dx.doi.org/10.1080/14734220601142878]. [PMID: 17853088].
[77]
Giustarini, D.; Milzani, A.; Dalle-Donne, I.; Tsikas, D.; Rossi, R. N-Acetylcysteine ethyl ester (NACET): a novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential. Biochem. Pharmacol., 2012, 84(11), 1522-1533. [http://dx.doi.org/10.1016/j.bcp.2012.09. 010]. [PMID: 23000913].
[78]
Sunitha, K.; Hemshekhar, M.; Thushara, R.M.; Santhosh, M.S.; Yariswamy, M.; Kemparaju, K.; Girish, K.S. N-Acetylcysteine amide: a derivative to fulfill the promises of N-Acetylcysteine. Free Radic. Res., 2013, 47(5), 357-367. [http://dx.doi.org/10.3109/ 10715762.2013.781595]. [PMID: 23472882].
[79]
Maddirala, Y.; Tobwala, S.; Ercal, N. N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line. Brain Res., 2015, 1608, 157-166. [http://dx.doi.org/10.1016/j.brainres. 2015.02.006]. [PMID: 25681547].
[80]
Halliwell, B.; Chirico, S. Lipid peroxidation: its mechanism, measurement, and significance Am. J. Clin. Nutr., 1993. 57(5 Suppl)(), 715S-724S. discussion 724S-725S
[81]
Alessandri, J.M.; Guesnet, P.; Vancassel, S.; Astorg, P.; Denis, I.; Langelier, B.; Aïd, S.; Poumès-Ballihaut, C.; Champeil-Potokar, G.; Lavialle, M. Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. Reprod. Nutr. Dev., 2004, 44(6), 509-538. [http://dx.doi. org/10.1051/rnd:2004063]. [PMID: 15762297].
[82]
Bayir, H.; Fadeel, B.; Palladino, M.J.; Witasp, E.; Kurnikov, I.V.; Tyurina, Y.Y.; Tyurin, V.A.; Amoscato, A.A.; Jiang, J.; Kochanek, P.M.; DeKosky, S.T.; Greenberger, J.S.; Shvedova, A.A.; Kagan, V.E. Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria. Biochim. Biophys. Acta, 2006, 1757(5-6), 648-659. [http://dx.doi.org/ 10.1016/j.bbabio.2006.03.002]. [PMID: 16740248].
[83]
Hill, S.; Lamberson, C.R.; Xu, L.; To, R.; Tsui, H.S.; Shmanai, V.V.; Bekish, A.V.; Awad, A.M.; Marbois, B.N.; Cantor, C.R.; Porter, N.A.; Clarke, C.F.; Shchepinov, M.S. Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation. Free Radic. Biol. Med., 2012, 53(4), 893-906. [http://dx.doi. org/10.1016/j.freeradbiomed.2012.06.004]. [PMID: 22705367].
[84]
Cotticelli, M.G.; Crabbe, A.M.; Wilson, R.B.; Shchepinov, M.S. Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids. Redox Biol., 2013, 1, 398-404. [http://dx.doi.org/10.1016/j.redox. 2013.06.004]. [PMID: 25499576].
[85]
Lagier-Tourenne, C.; Tazir, M.; López, L.C.; Quinzii, C.M.; Assoum, M.; Drouot, N.; Busso, C.; Makri, S.; Ali-Pacha, L.; Benhassine, T.; Anheim, M.; Lynch, D.R.; Thibault, C.; Plewniak, F.; Bianchetti, L.; Tranchant, C.; Poch, O.; DiMauro, S.; Mandel, J.L.; Barros, M.H.; Hirano, M.; Koenig, M. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am. J. Hum. Genet., 2008, 82(3), 661-672. [http://dx.doi.org/10.1016/j.ajhg.2007.12.024]. [PMID: 18319074].
[86]
Mignot, C.; Apartis, E.; Durr, A.; Marques Lourenço, C.; Charles, P.; Devos, D.; Moreau, C.; de Lonlay, P.; Drouot, N.; Burglen, L.; Kempf, N.; Nourisson, E.; Chantot-Bastaraud, S.; Lebre, A.S.; Rio, M.; Chaix, Y.; Bieth, E.; Roze, E.; Bonnet, I.; Canaple, S.; Rastel, C.; Brice, A.; Rötig, A.; Desguerre, I.; Tranchant, C.; Koenig, M.; Anheim, M. Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression. Orphanet J. Rare Dis., 2013, 8(1), 173. [http://dx.doi.org/10.1186/1750-1172-8-173]. [PMID: 24164873].
[87]
Hikmat, O.; Tzoulis, C.; Knappskog, P.M.; Johansson, S.; Boman, H.; Sztromwasser, P.; Lien, E.; Brodtkorb, E.; Ghezzi, D.; Bindoff, L.A. ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic? Eur. J. Neurol., 2016, 23(7), 1188-1194. [http://dx.doi.org/10.1111/ene.13003]. [PMID: 27106809].
[88]
Barca, E.; Musumeci, O.; Montagnese, F.; Marino, S.; Granata, F.; Nunnari, D.; Peverelli, L.; DiMauro, S.; Quinzii, C.M.; Toscano, A. Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. Clin. Genet., 2016, 90(2), 156-160. [http://dx.doi.org/10.1111/cge.12742]. [PMID: 26818466].
[89]
Liu, Y.T.; Hersheson, J.; Plagnol, V.; Fawcett, K.; Duberley, K.E.; Preza, E.; Hargreaves, I.P.; Chalasani, A.; Laurá, M.; Wood, N.W.; Reilly, M.M.; Houlden, H. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation. J. Neurol. Neurosurg. Psychiatry, 2014, 85(5), 493-498. [http://dx.doi.org/10. 1136/jnnp-2013-306483]. [PMID: 24218524].
[90]
Blumkin, L.; Leshinsky-Silver, E.; Zerem, A.; Yosovich, K.; Lerman-Sagie, T.; Lev, D. Heterozygous mutations in the ADCK3 gene in siblings with cerebellar atrophy and extreme phenotypic variability. JIMD Rep., 2014, 12, 103-107. [http://dx.doi.org/10. 1007/8904_2013_251]. [PMID: 24048965].
[91]
Acosta, M.J.; Vazquez Fonseca, L.; Desbats, M.A.; Cerqua, C.; Zordan, R.; Trevisson, E.; Salviati, L. Coenzyme Q biosynthesis in health and disease. Biochim. Biophys. Acta, 2016, 1857(8), 1079-1085.
[92]
Stefely, J.A.; Licitra, F.; Laredj, L.; Reidenbach, A.G.; Kemmerer, Z.A.; Grangeray, A.; Jaeg-Ehret, T.; Minogue, C.E.; Ulbrich, A.; Hutchins, P.D.; Wilkerson, E.M.; Ruan, Z.; Aydin, D.; Hebert, A.S.; Guo, X.; Freiberger, E.C.; Reutenauer, L.; Jochem, A.; Chergova, M.; Johnson, I.E.; Lohman, D.C.; Rush, M.J.P.; Kwiecien, N.W.; Singh, P.K.; Schlagowski, A.I.; Floyd, B.J.; Forsman, U.; Sindelar, P.J.; Westphall, M.S.; Pierrel, F.; Zoll, J.; Dal Peraro, M.; Kannan, N.; Bingman, C.A.; Coon, J.J.; Isope, P.; Puccio, H. pagliarini, D.J. Cerebellar ataxia and coenzyme Q deficiency through loss of unorthodox kinase. Mol. Cell, 2016, 63(4), 608-620. [http:// dx.doi.org/10.1016/j.molcel.2016.06.030]. [PMID: 27499294].
[93]
Ziosi, M.; Di Meo, I.; Kleiner, G.; Gao, X.H.; Barca, E.; Sanchez-Quintero, M.J.; Tadesse, S.; Jiang, H.; Qiao, C.; Rodenburg, R.J.; Scalais, E.; Schuelke, M.; Willard, B.; Hatzoglou, M.; Tiranti, V.; Quinzii, C.M. Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. EMBO Mol. Med., 2017, 9(1), 96-111. [http://dx.doi.org/10.15252/emmm.201606356]. [PMID: 27856618].
[94]
Luna-Sánchez, M.; Díaz-Casado, E.; Barca, E.; Tejada, M.A.; Montilla-García, Á.; Cobos, E.J.; Escames, G.; Acuña-Castroviejo, D.; Quinzii, C.M.; López, L.C. The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene. EMBO Mol. Med., 2015, 7(5), 670-687. [http://dx. doi.org/10.15252/emmm.201404632]. [PMID: 25802402].
[95]
García-Corzo, L.; Luna-Sánchez, M.; Doerrier, C.; Ortiz, F.; Escames, G.; Acuña-Castroviejo, D.; López, L.C. Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency. Biochim. Biophys. Acta, 2014, 1842(7), 893-901. [http://dx. doi.org/10.1016/j.bbadis.2014.02.008]. [PMID: 24576561].
[96]
Ben, H.C.; Doerflinger, N.; Belal, S.; Linder, C.; Reutenauer, L.; Dib, C.; Gyapay, G.; Vignal, A.; Le Paslier, D.; Cohen, D. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping. Nat. Genet., 1993, 5(2), 195-200. [http://dx.doi.org/10.1038/ng1093-195]. [PMID: 8252047].
[97]
El Euch-Fayache, G.; Bouhlal, Y.; Amouri, R.; Feki, M.; Hentati, F. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency. Brain, 2014, 137(Pt 2), 402-410. [http://dx.doi.org/10.1093/brain/awt339]. [PMID: 24369383].
[98]
Dürr, A.; Cossee, M.; Agid, Y.; Campuzano, V.; Mignard, C.; Penet, C.; Mandel, J.L.; Brice, A.; Koenig, M. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N. Engl. J. Med., 1996, 335(16), 1169-1175. [http://dx.doi.org/10.1056/NEJM 199610173351601]. [PMID: 8815938].
[99]
Campuzano, V.; Montermini, L.; Moltò, M.D.; Pianese, L.; Cossée, M.; Cavalcanti, F.; Monros, E.; Rodius, F.; Duclos, F.; Monticelli, A.; Zara, F.; Cañizares, J.; Koutnikova, H.; Bidichandani, S.I.; Gellera, C.; Brice, A.; Trouillas, P.; De Michele, G.; Filla, A.; De Frutos, R.; Palau, F.; Patel, P.I.; Di Donato, S.; Mandel, J.L.; Cocozza, S.; Koenig, M.; Pandolfo, M. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science, 1996, 271(5254), 1423-1427. [http://dx.doi.org/10. 1126/science.271.5254.1423]. [PMID: 8596916].
[100]
Campuzano, V.; Montermini, L.; Lutz, Y.; Cova, L.; Hindelang, C.; Jiralerspong, S.; Trottier, Y.; Kish, S.J.; Faucheux, B.; Trouillas, P.; Authier, F.J.; Dürr, A.; Mandel, J.L.; Vescovi, A.; Pandolfo, M.; Koenig, M. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum. Mol. Genet., 1997, 6(11), 1771-1780. [http://dx.doi.org/10.1093/hmg/6.11.1771]. [PMID: 9302253].
[101]
Mariotti, C.; Solari, A.; Torta, D.; Marano, L.; Fiorentini, C.; Di Donato, S. Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial. Neurology, 2003, 60(10), 1676-1679. [http://dx.doi.org/10.1212/01.WNL.0000055872.50364. FC]. [PMID: 12771264].
[102]
Weidemann, F.; Rummey, C.; Bijnens, B.; Störk, S.; Jasaityte, R.; Dhooge, J.; Baltabaeva, A.; Sutherland, G.; Schulz, J.B.; Meier, T. The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms. Circulation, 2012, 125(13), 1626-1634. [http://dx.doi.org/10.1161/ CIRCULATIONAHA.111.059477]. [PMID: 22379112].
[103]
Cooper, J.M.; Korlipara, L.V.; Hart, P.E.; Bradley, J.L.; Schapira, A.H. Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy. Eur. J. Neurol., 2008, 15(12), 1371-1379. [http://dx.doi.org/ 10.1111/j.1468-1331.2008.02318.x]. [PMID: 19049556].
[104]
Kearney, M.; Orrell, R.W.; Fahey, M.; Brassington, R.; Pandolfo, M. Pharmacological treatments for Friedreich ataxia. Cochrane Database Syst. Rev., 2016, (8), CD007791. [PMID: 27572719].
[105]
Lynch, D.R.; Perlman, S.L.; Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch. Neurol., 2010, 67(8), 941-947. [http://dx.doi.org/10.1001/archneurol. 2010.168]. [PMID: 20697044].
[106]
Bird, T.D. Hereditary Ataxia Overview.In GeneReviews(R), 1993, 2016.
[107]
Durr, A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol., 2010, 9(9), 885-894. [http:// dx.doi.org/10.1016/S1474-4422(10)70183-6]. [PMID: 20723845].
[108]
Lo, R.Y.; Figueroa, K.P.; Pulst, S.M.; Lin, C.Y.; Perlman, S.; Wilmot, G.; Gomez, C.; Schmahmann, J.; Paulson, H.; Shakkottai, V.G.; Ying, S.; Zesiewicz, T.; Bushara, K.; Geschwind, M.; Xia, G.; Subramony, S.H.; Ashizawa, T.; Kuo, S.H. Coenzyme Q10 and spinocerebellar ataxias. Mov. Disord., 2015, 30(2), 214-220. [http://dx.doi.org/10.1002/mds.26088]. [PMID: 25449974].
[109]
Stucki, D.M.; Ruegsegger, C.; Steiner, S.; Radecke, J.; Murphy, M.P.; Zuber, B.; Saxena, S. Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ. Free Radic. Biol. Med., 2016, 97, 427-440. [http://dx.doi.org/10.1016/j.freeradbiomed. 2016.07.005]. [PMID: 27394174].
[110]
Gatti, R.A.; Berkel, I.; Boder, E.; Braedt, G.; Charmley, P.; Concannon, P.; Ersoy, F.; Foroud, T.; Jaspers, N.G.; Lange, K. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature, 1988, 336(6199), 577-580. [http://dx.doi.org/10.1038/ 336577a0]. [PMID: 3200306].
[111]
Maciejczyk, M.; Mikoluc, B.; Pietrucha, B.; Heropolitanska-Pliszka, E.; Pac, M.; Motkowski, R.; Car, H. Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome. Redox Biol., 2017, 11, 375-383. [http://dx.doi.org/10.1016/j.redox. 2016.12.030]. [PMID: 28063379].
[112]
Weyemi, U.; Redon, C.E.; Aziz, T.; Choudhuri, R.; Maeda, D.; Parekh, P.R.; Bonner, M.Y.; Arbiser, J.L.; Bonner, W.M. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease. Proc. Natl. Acad. Sci. USA, 2015, 112(7), 2121-2126. [http://dx. doi.org/10.1073/pnas.1418139112]. [PMID: 25646414].
[113]
Pagano, G.; Talamanca, A.A.; Castello, G.; Cordero, M.D.; d’Ischia, M.; Gadaleta, M.N.; Pallardó, F.V.; Petrović, S.; Tiano, L.; Zatterale, A. Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies. Oxid. Med. Cell. Longev., 2014, 2014, 541230. [http://dx.doi.org/10.1155/2014/541230]. [PMID: 24876913].
[114]
Reichenbach, J.; Schubert, R.; Schwan, C.; Müller, K.; Böhles, H.J.; Zielen, S. Anti-oxidative capacity in patients with ataxia telangiectasia. Clin. Exp. Immunol., 1999, 117(3), 535-539. [http:// dx.doi.org/10.1046/j.1365-2249.1999.01000.x]. [PMID: 10469059].
[115]
Degan, P.; d’Ischia, M.; Pallardó, F.V.; Zatterale, A.; Brusco, A.; Calzone, R.; Cavalieri, S.; Kavakli, K.; Lloret, A.; Manini, P.; Pisanti, M.A.; Vuttariello, E.; Pagano, G. Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. Clin. Biochem., 2007, 40(9-10), 666-670. [http://dx.doi.org/10.1016/j.clinbiochem.2007.03.013]. [PMID: 17466964].
[116]
Reliene, R.; Schiestl, R.H. Experimental antioxidant therapy in ataxia telangiectasia. Clin. Med. Oncol., 2008, 2, 431-436. [http://dx.doi.org/10.4137/CMO.S535]. [PMID: 21892312].
[117]
Date, H.; Onodera, O.; Tanaka, H.; Iwabuchi, K.; Uekawa, K.; Igarashi, S.; Koike, R.; Hiroi, T.; Yuasa, T.; Awaya, Y.; Sakai, T.; Takahashi, T.; Nagatomo, H.; Sekijima, Y.; Kawachi, I.; Takiyama, Y.; Nishizawa, M.; Fukuhara, N.; Saito, K.; Sugano, S.; Tsuji, S. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat. Genet., 2001, 29(2), 184-188. [http://dx.doi.org/10.1038/ng1001-184]. [PMID: 11586299].
[118]
Moreira, M.C.; Barbot, C.; Tachi, N.; Kozuka, N.; Uchida, E.; Gibson, T.; Mendonça, P.; Costa, M.; Barros, J.; Yanagisawa, T.; Watanabe, M.; Ikeda, Y.; Aoki, M.; Nagata, T.; Coutinho, P.; Sequeiros, J.; Koenig, M. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat. Genet., 2001, 29(2), 189-193. [http://dx.doi.org/10.1038/ng1001-189]. [PMID: 11586300].
[119]
Castellotti, B.; Mariotti, C.; Rimoldi, M.; Fancellu, R.; Plumari, M.; Caimi, S.; Uziel, G.; Nardocci, N.; Moroni, I.; Zorzi, G.; Pareyson, D.; Di Bella, D.; Di Donato, S.; Taroni, F.; Gellera, C. Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. Neurogenetics, 2011, 12(3), 193-201. [http://dx. doi.org/10.1007/s10048-011-0281-x]. [PMID: 21465257].
[120]
Gueven, N.; Becherel, O.J.; Kijas, A.W.; Chen, P.; Howe, O.; Rudolph, J.H.; Gatti, R.; Date, H.; Onodera, O.; Taucher-Scholz, G.; Lavin, M.F. Aprataxin, a novel protein that protects against genotoxic stress. Hum. Mol. Genet., 2004, 13(10), 1081-1093. [http://dx.doi.org/10.1093/hmg/ddh122]. [PMID: 15044383].
[121]
Musumeci, O.; Naini, A.; Slonim, A.E.; Skavin, N.; Hadjigeorgiou, G.L.; Krawiecki, N.; Weissman, B.M.; Tsao, C.Y.; Mendell, J.R.; Shanske, S.; De Vivo, D.C.; Hirano, M.; DiMauro, S. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology, 2001, 56(7), 849-855. [http://dx.doi.org/10.1212/WNL.56. 7.849]. [PMID: 11294920].
[122]
Sykora, P.; Croteau, D.L.; Bohr, V.A.; Wilson, D.M., III Aprataxin localizes to mitochondria and preserves mitochondrial function. Proc. Natl. Acad. Sci. USA, 2011, 108(18), 7437-7442. [http://dx. doi.org/10.1073/pnas.1100084108]. [PMID: 21502511].
[123]
Garcia-Diaz, B.; Barca, E.; Balreira, A.; Lopez, L.C.; Tadesse, S.; Krishna, S.; Naini, A.; Mariotti, C.; Castellotti, B.; Quinzii, C.M. Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway. Hum. Mol. Genet., 2015, 24(16), 4516-4529. [http://dx.doi.org/10.1093/hmg/ddv183]. [PMID: 25976310].
[124]
Gilman, S.; Wenning, G.K.; Low, P.A.; Brooks, D.J.; Mathias, C.J.; Trojanowski, J.Q.; Wood, N.W.; Colosimo, C.; Dürr, A.; Fowler, C.J.; Kaufmann, H.; Klockgether, T.; Lees, A.; Poewe, W.; Quinn, N.; Revesz, T.; Robertson, D.; Sandroni, P.; Seppi, K.; Vidailhet, M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology, 2008, 71(9), 670-676. [http://dx.doi. org/10.1212/01.wnl.0000324625.00404.15]. [PMID: 18725592].
[125]
Cykowski, M.D.; Coon, E.A.; Powell, S.Z.; Jenkins, S.M.; Benarroch, E.E.; Low, P.A.; Schmeichel, A.M.; Parisi, J.E. Expanding the spectrum of neuronal pathology in multiple system atrophy. Brain, 2015, 138(Pt 8), 2293-2309. [http://dx.doi.org/10.1093/ brain/awv114]. [PMID: 25981961].
[126]
Fernagut, P.O.; Dehay, B.; Maillard, A.; Bezard, E.; Perez, P.; Pavy-Le Traon, A.; Rascol, O.; Foubert-Samier, A.; Tison, F.; Meissner, W.G. Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies. Neurobiol. Dis., 2014, 67, 133-139. [http://dx.doi.org/10.1016/j.nbd.2014.03. 021]. [PMID: 24727096].
[127]
Schottlaender, L.V.; Houlden, H. Mutant COQ2 in multiple-system atrophy. N. Engl. J. Med., 2014, 371(1), 81. [PMID: 24988569].
[128]
Multiple-system atrophy research collaboration. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N. Engl. J. Med., 2013, 369(3), 233-244. [http://dx.doi.org/10.1056/NEJMoa 1212115]. [PMID: 23758206].
[129]
Sailer, A.; Scholz, S.W.; Nalls, M.A.; Schulte, C.; Federoff, M.; Price, T.R.; Lees, A.; Ross, O.A.; Dickson, D.W.; Mok, K.; Mencacci, N.E.; Schottlaender, L.; Chelban, V.; Ling, H.; O’Sullivan, S.S.; Wood, N.W.; Traynor, B.J.; Ferrucci, L.; Federoff, H.J.; Mhyre, T.R.; Morris, H.R.; Deuschl, G.; Quinn, N.; Widner, H.; Albanese, A.; Infante, J.; Bhatia, K.P.; Poewe, W.; Oertel, W.; Höglinger, G.U.; Wüllner, U.; Goldwurm, S.; Pellecchia, M.T.; Ferreira, J.; Tolosa, E.; Bloem, B.R.; Rascol, O.; Meissner, W.G.; Hardy, J.A.; Revesz, T.; Holton, J.L.; Gasser, T.; Wenning, G.K.; Singleton, A.B.; Houlden, H. A genome-wide association study in multiple system atrophy. Neurology, 2016, 87(15), 1591-1598. [http:// dx.doi.org/10.1212/WNL.0000000000003221]. [PMID: 27629089].
[130]
Mitsui, J.; Matsukawa, T.; Yasuda, T.; Ishiura, H.; Tsuji, S. Plasma Coenzyme Q10 levels in patients with multiple system atrophy. JAMA Neurol., 2016, 73(8), 977-980. [http://dx.doi.org/10.1001/ jamaneurol.2016.1325]. [PMID: 27356913].

Rights & Permissions Print Cite
Article Metrics
38
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy