Edaravone May Prevent Ferroptosis in ALS

Author(s): Snežana Spasić*, Aleksandra Nikolić-Kokić, Srđan Miletić, Zorana Oreščanin-Dušić, Mihajlo B. Spasić, Duško Blagojević, Zorica Stević

Journal Name: Current Drug Targets

Volume 21 , Issue 8 , 2020

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Abstract:

Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons. Mutations and biochemical changes in various cell types jointly contribute to motor neuron death, disease onset, and disease progression. The overall mechanism of neurodegeneration in ALS is still not completely understood. Dying motor neurons have been reported to exhibit features of apoptosis. However, non-apoptotic features of dying motor neurons have also been reported such as ferroptosis. The role of Edaravone in the prevention of ferroptosis in parallel with other therapeutic approaches to ALS therapy is discussed.

Keywords: Edaravone, amyotrophic lateral sclerosis (ALS), ferroptosis, therapy, neurons, neurodegeneration.

[1]
Cozzolino M, Ferri A, Carrì MT. Amyotrophic lateral sclerosis: from current developments in the laboratory to clinical implications. Antioxid Redox Signal 2008; 10(3): 405-43.
[http://dx.doi.org/10.1089/ars.2007.1760] [PMID: 18370853]
[2]
Musarò A. Understanding ALS: new therapeutic approaches. FEBS J 2013; 280(17): 4315-22.
[http://dx.doi.org/10.1111/febs.12087] [PMID: 23217177]
[3]
Silani V, Ludolph A, Fornai F. The emerging picture of ALS: a multisystem, not only a "motor neuron disease. Arch Ital Biol 2017; 155(4): 99-109.
[PMID: 29405027]
[4]
Frakes AE, Braun L, Ferraiuolo L, Guttridge DC, Kaspar BK. Additive amelioration of ALS by co-targeting independent pathogenic mechanisms. Ann Clin Transl Neurol 2017; 4(2): 76-86.
[http://dx.doi.org/10.1002/acn3.375] [PMID: 28168207]
[5]
Spasojević I, Mojović M, Stević Z, et al. Bioavailability and catalytic properties of copper and iron for Fenton chemistry in human cerebrospinal fluid. Redox Rep 2010; 15((1):): 29-- 35. a.
[http://dx.doi.org/10.1179/174329210X12650506623087] [PMID: 20196926]
[6]
Ignjatović A, Stević Z, Lavrnić S, Daković M, Bačić G. Brain iron MRI: a biomarker for amyotrophic lateral sclerosis. J Magn Reson Imaging 2013; 38(6): 1472-9.
[http://dx.doi.org/10.1002/jmri.24121] [PMID: 23564606]
[7]
Acosta-Cabronero J, Machts J, Schreiber S, et al. Quantitative susceptibility MRI to detect brain iron in amyotrophic lateral sclerosis. Radiology 2018; 289(1): 195-203.
[http://dx.doi.org/10.1148/radiol.2018180112] [PMID: 30040038]
[8]
Hadzhieva M, Kirches E, Wilisch-Neumann A, et al. Dysregulation of iron protein expression in the G93A model of amyotrophic lateral sclerosis. Neuroscience 2013; 230: 94-101.
[http://dx.doi.org/10.1016/j.neuroscience.2012.11.021] [PMID: 23178912]
[9]
Moreau C, Danel V, Devedjian JC, et al. Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis? Antioxid Redox Signal 2018; 29(8): 742-8.
[http://dx.doi.org/10.1089/ars.2017.7493] [PMID: 29287521]
[10]
Desnuelle C, Dib M, Garrel C, Favier A. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph Lateral Scler Other Motor Neuron Disord 2001; 2(1): 9-18.
[http://dx.doi.org/10.1080/146608201300079364] [PMID: 11465936]
[11]
Apostolski S, Marinković Z, Nikolić A, Blagojević D, Spasić MB, Michelson AM. Glutathione peroxidase in amyotrophic lateral sclerosis: the effects of selenium supplementation. J Environ Pathol Toxicol Oncol 1998; 17(3-4): 325-9.
[PMID: 9726810]
[12]
Stojsavljević A, Jagodić J, Vujotić L, et al. Reference values for trace essential elements in the whole blood and serum samples of the adult Serbian population: significance of selenium deficiency. Environ Sci Pollut Res Int 2020; 27(2): 1397-405.
[http://dx.doi.org/10.1007/s11356-019-06936-8] [PMID: 31748992]
[13]
Conrad M, Schneider M, Seiler A, Bornkamm GW. Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. Biol Chem 2007; 388(10): 1019-25.
[http://dx.doi.org/10.1515/BC.2007.130] [PMID: 17937615]
[14]
Yamamoto Y, Kuwahara T, Watanabe K, Watanabe K. Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep 1996; 2(5): 333-8.
[http://dx.doi.org/10.1080/13510002.1996.11747069] [PMID: 27406414]
[15]
Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev 2006; 12(1): 9-20.
[http://dx.doi.org/10.1111/j.1527-3458.2006.00009.x] [PMID: 16834755]
[16]
Watanabe K, Tanaka M, Yuki S, Hirai M, Yamamoto Y. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J Clin Biochem Nutr 2018; 62(1): 20-38.
[http://dx.doi.org/10.3164/jcbn.17-62] [PMID: 29371752]
[17]
Yamamoto Y. Plasma marker of tissue oxidative damage and edaravone as a scavenger drug against peroxyl radicals and peroxynitrite. J Clin Biochem Nutr 2017; 60(1): 49-54.
[http://dx.doi.org/10.3164/jcbn.16-63] [PMID: 28163382]
[18]
Abe S, Kirima K, Tsuchiya K, et al. The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical. Chem Pharm Bull (Tokyo) 2004; 52(2): 186-91.
[http://dx.doi.org/10.1248/cpb.52.186] [PMID: 14758002]
[19]
Wang H, Kozekov ID, Harris TM, Rizzo CJ. Site-specific synthesis and reactivity of oligonucleotides containing stereochemically defined 1,N2-deoxyguanosine adducts of the lipid peroxidation product trans-4-hydroxynonenal. J Am Chem Soc 2003; 125(19): 5687-700.
[http://dx.doi.org/10.1021/ja0288800] [PMID: 12733907]
[20]
Higashi Y, Jitsuiki D, Chayama K, Yoshizumi M. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger, for treatment of cardiovascular diseases. Recent Pat Cardiovasc Drug Discov 2006; 1(1): 85-93.
[http://dx.doi.org/10.2174/157489006775244191] [PMID: 18221078]
[21]
Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke 2005; 36(10): 2220-5.
[http://dx.doi.org/10.1161/01.STR.0000182241.07096.06] [PMID: 16166574]
[22]
Jin YJ, Mima T, Raicu V, Park KC, Shimizu K. Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils. Neurosci Res 2002; 43(1): 75-9.
[http://dx.doi.org/10.1016/S0168-0102(02)00019-6] [PMID: 12074843]
[23]
Nakamura T, Kuroda Y, Yamashita S, et al. Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke 2008; 39(2): 463-9.
[http://dx.doi.org/10.1161/STROKEAHA.107.486654] [PMID: 18096835]
[24]
Ohta M, Higashi Y, Yawata T, et al. Attenuation of axonal injury and oxidative stress by edaravone protects against cognitive impairments after traumatic brain injury. Brain Res 2013; 1490: 184-92.
[http://dx.doi.org/10.1016/j.brainres.2012.09.011] [PMID: 22982593]
[25]
Lapchak PA. A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy? Expert Opin Pharmacother 2010; 11(10): 1753-63.
[http://dx.doi.org/10.1517/14656566.2010.493558] [PMID: 20491547]
[26]
Homma T, Kobayashi S, Sato H, Fujii J. Edaravone, a free radical scavenger, protects against ferroptotic cell death in vitro. Exp Cell Res 2019; 384(1)111592
[http://dx.doi.org/10.1016/j.yexcr.2019.111592] [PMID: 31479686]
[27]
Abraham A, Nefussy B, Fainmesser Y, Ebrahimi Y, Karni A, Drory VE. Early post-marketing experience with edaravone in an unselected group of patients with ALS. Amyotroph Lateral Scler Frontotemporal Degener 2019; 20(3-4): 260-3.
[http://dx.doi.org/10.1080/21678421.2019.1572191] [PMID: 30784320]
[28]
Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15(7-8): 610-7.
[http://dx.doi.org/10.3109/21678421.2014.959024] [PMID: 25286015]
[29]
Abe K, Aoki M, Tsuji S, et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16(7): 505-12.
[http://dx.doi.org/10.1016/S1474-4422(17)30115-1] [PMID: 28522181]
[30]
Spasojević I, Stević Z, Nikolić-Kokić A, Jones DR, Blagojević D, Spasić MB. Different roles of radical scavengers--ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Redox Rep 2010; 15(2): 81-6.
[http://dx.doi.org/10.1179/174329210X12650506623320] [PMID: 20500989]
[31]
Paganoni S, Nicholson K, Chan J, et al. Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database. Muscle Nerve 2018; 57(3): 430-4.
[http://dx.doi.org/10.1002/mus.25950] [PMID: 28857199]
[32]
O’Reilly EJ, Liu D, Johns DR, et al. Serum urate at trial entry and ALS progression in EMPOWER. Amyotroph Lateral Scler Frontotemporal Degener 2017; 18(1-2): 120-5.
[http://dx.doi.org/10.1080/21678421.2016.1214733] [PMID: 27677562]
[33]
Paganoni S, Zhang M, Quiroz Zárate A, et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis. J Neurol 2012; 259(9): 1923-8.
[http://dx.doi.org/10.1007/s00415-012-6440-7] [PMID: 22323210]
[34]
Bakshi R, Zhang H, Logan R, et al. Neuroprotective effects of urate are mediated by augmenting astrocytic glutathione synthesis and release. Neurobiol Dis 2015; 82: 574-9.
[http://dx.doi.org/10.1016/j.nbd.2015.08.022] [PMID: 26341543]
[35]
Du Y, Chen CP, Tseng CY, Eisenberg Y, Firestein BL. Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity. Glia 2007; 55(5): 463-72.
[http://dx.doi.org/10.1002/glia.20472] [PMID: 17203476]
[36]
Nicholson K, Chan J, Macklin EA, et al. Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis. Ann Clin Transl Neurol 2018; 5(12): 1522-33.
[http://dx.doi.org/10.1002/acn3.671] [PMID: 30564619]
[37]
Xiao B, Bi FF, Hu YQ, et al. Edaravone neuroprotection effected by suppressing the gene expression of the Fas signal pathway following transient focal ischemia in rats. Neurotox Res 2007; 12(3): 155-62.
[http://dx.doi.org/10.1007/BF03033912] [PMID: 17967739]
[38]
Ignjatović A, Stević Z, Lavrnić D, et al. Inappropriately chelated iron in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler 2012; 13(4): 357-62.
[http://dx.doi.org/10.3109/17482968.2012.665929] [PMID: 22424123]
[39]
Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress? J Neurol Sci 2009; 285(1-2): 95-9.
[http://dx.doi.org/10.1016/j.jns.2009.06.002] [PMID: 19552925]
[40]
Nikolić-Kokić A, Oreščanin-Dušić Z, Slavić M, et al. The effects of human wild-type and FALS mutant L144P SOD1 on non-vascular smooth muscle contractions. J Med Biochem 2013; 32: 375-9.
[http://dx.doi.org/10.2478/jomb-2013-0032]
[41]
Allen MJ, Lacroix JJ, Ramachandran S, et al. Mutant SOD1 forms ion channel: implications for ALS pathophysiology. Neurobiol Dis 2012; 45(3): 831-8.
[http://dx.doi.org/10.1016/j.nbd.2011.08.031] [PMID: 21930207]
[42]
McAlary L, Plotkin SS, Yerbury JJ, Cashman NR. Prion-Like Propagation of Protein Misfolding and Aggregation in Amyotrophic Lateral Sclerosis. Front Mol Neurosci 2019; 12: 262.
[http://dx.doi.org/10.3389/fnmol.2019.00262] [PMID: 31736708]
[43]
Chen L, Hambright WS, Na R, Ran Q. ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis. J Biol Chem 2015; 290(47): 28097-106.
[http://dx.doi.org/10.1074/jbc.M115.680090] [PMID: 26400084]


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VOLUME: 21
ISSUE: 8
Year: 2020
Page: [776 - 780]
Pages: 5
DOI: 10.2174/1389450121666200220123305
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