{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:50:31Z","timestamp":1791946231985,"version":"4.3.4"},"reference-count":151,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["PN-III-P1-1.1-TE-2021-0960"],"award-info":[{"award-number":["PN-III-P1-1.1-TE-2021-0960"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. In spite of intensive research to discover the underlying mechanisms, the results are fairly inconclusive. Multiple hypotheses have been regarded, including genetic, molecular, and cellular processes. Notably, oxidative stress has been demonstrated to play a crucial role in ALS pathogenesis. In addition to already recognized and exhaustively studied genetic mutations involved in oxidative stress production, exposure to various environmental factors (e.g., electromagnetic fields, solvents, pesticides, heavy metals) has been suggested to enhance oxidative damage. This review aims to describe the main processes influenced by the most frequent genetic mutations and environmental factors concurring in oxidative stress occurrence in ALS and the potential therapeutic molecules capable of diminishing the ALS related pro-oxidative status.<\/jats:p>","DOI":"10.3390\/ijms23169339","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Oxidative Stress in Amyotrophic Lateral Sclerosis: Synergy of Genetic and Environmental Factors"],"prefix":"10.3390","volume":"23","author":[{"given":"Anca","family":"Motataianu","sequence":"first","affiliation":[{"name":"Department of Neurology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540136 Targu Mures, Romania"},{"name":"1st Neurology Clinic, Emergency Clinical County Hospital Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-2177","authenticated-orcid":false,"given":"Georgiana","family":"Serban","sequence":"additional","affiliation":[{"name":"Doctoral School, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barcutean","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540136 Targu Mures, Romania"},{"name":"1st Neurology Clinic, Emergency Clinical County Hospital Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodica","family":"Balasa","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540136 Targu Mures, Romania"},{"name":"1st Neurology Clinic, Emergency Clinical County Hospital Targu Mures, 540136 Targu Mures, Romania"},{"name":"Doctoral School, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_2","first-page":"181","article-title":"Risk factors for amyotrophic lateral sclerosis","volume":"7","author":"Ingre","year":"2015","journal-title":"Clin. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-981-13-8367-0_5","article-title":"Crosstalk Between Oxidative Stress and Mitochondrial Damage: Focus on Amyotrophic Lateral Sclerosis","volume":"1158","author":"Greco","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(17)31287-4","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"Hardiman","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S1474-4422(13)70036-X","article-title":"Controversies and priorities in amyotrophic lateral sclerosis","volume":"12","author":"Turner","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/bs.pmch.2018.12.001","article-title":"Amyotrophic lateral sclerosis","volume":"58","author":"Valko","year":"2019","journal-title":"Prog. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1089\/ars.2017.7321","article-title":"Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities","volume":"30","author":"Sbodio","year":"2019","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.bbabio.2015.05.022","article-title":"Mitochondrial dysfunction in aging: Much progress but many unresolved questions","volume":"1847","author":"Payne","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","first-page":"5021694","article-title":"Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention","volume":"15","author":"Montezinho","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_11","first-page":"41","article-title":"Oxidative stress and mitochondrial damage: Importance in non-SOD1 ALS","volume":"9","author":"Valle","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kausar, S., Wang, F., and Cui, H. (2018). The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases. Cells, 7.","DOI":"10.3390\/cells7120274"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.exger.2010.01.003","article-title":"The sites and topology of mitochondrial superoxide production","volume":"45","author":"Brand","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"646354","DOI":"10.1155\/2012\/646354","article-title":"Oxidative stress, mitochondrial dysfunction, and aging","volume":"2012","author":"Cui","year":"2012","journal-title":"J. Signal. Transduct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1007\/s12035-015-9337-5","article-title":"Oxidative Stress in Neurodegenerative Diseases","volume":"53","author":"Niedzielska","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1080\/14660820310011278","article-title":"Relevance of oxidative injury in the pathogenesis of motor neuron diseases","volume":"4","author":"Agar","year":"2003","journal-title":"Amyotroph. Lateral. Scler. Other Motor. Neuron. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vande Velde, C., McDonald, K.K., Boukhedimi, Y., McAlonis-Downes, M., Lobsiger, C.S., Bel Hadj, S., Zandona, A., Julien, J.P., Shah, S.B., and Cleveland, D.W. (2011). Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022031"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.expneurol.2007.05.026","article-title":"Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1","volume":"207","author":"Kraft","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.neuint.2008.01.009","article-title":"Oxidant-antioxidant imbalance in the erythrocytes of sporadic amyotrophic lateral sclerosis patients correlates with the progression of disease","volume":"52","author":"Babu","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.freeradbiomed.2013.06.029","article-title":"Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis","volume":"65","author":"Santella","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00401-019-01989-y","article-title":"ALS\/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response","volume":"138","author":"Anderson","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1093\/brain\/awu138","article-title":"A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement","volume":"137 Pt. 8","author":"Bannwarth","year":"2014","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"58","DOI":"10.15252\/emmm.201505496","article-title":"CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis","volume":"8","author":"Genin","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_26","first-page":"126","article-title":"Mechanisms of mutant SOD1 induced mitochondrial toxicity in amyotrophic lateral sclerosis","volume":"8","author":"Koistinaho","year":"2014","journal-title":"Front. Cell Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1093\/hmg\/ddn226","article-title":"Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria","volume":"17","author":"Kawamata","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3389\/fncel.2015.00336","article-title":"SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis","volume":"9","author":"Tafuri","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00401-004-0939-7","article-title":"Ultrastructural study of aggregates in the spinal cord of transgenic mice with a G93A mutant SOD1 gene","volume":"109","author":"Sasaki","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"RC215","DOI":"10.1523\/JNEUROSCI.22-06-j0001.2002","article-title":"Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS","volume":"22","author":"Higgins","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1089\/ars.2013.5385","article-title":"Regulation of CuZnSOD and its redox signaling potential: Implications for amyotrophic lateral sclerosis","volume":"20","author":"Hitchler","year":"2014","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.bbadis.2006.03.008","article-title":"Oxidative stress in ALS: A mechanism of neurodegeneration and a therapeutic target","volume":"1762","author":"Barber","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"28648","DOI":"10.1074\/jbc.M600138200","article-title":"The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu,Zn superoxide dismutase","volume":"281","author":"Carroll","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2004.06.021","article-title":"Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria","volume":"43","author":"Pasinelli","year":"2004","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105050","DOI":"10.1016\/j.nbd.2020.105050","article-title":"An ALS-linked mutation in TDP-43 disrupts normal protein interactions in the motor neuron response to oxidative stress","volume":"144","author":"Feneberg","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41467-017-00062-0","article-title":"Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation","volume":"8","author":"Afroz","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3389\/fncel.2015.00423","article-title":"Alterations in stress granule dynamics driven by TDP-43 and FUS: A link to pathological inclusions in ALS?","volume":"9","author":"Aulas","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00401-016-1575-8","article-title":"Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways","volume":"132","author":"Blokhuis","year":"2016","journal-title":"Acta. Neuropathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.adgen.2015.07.001","article-title":"Functional Significance of TDP-43 Mutations in Disease","volume":"91","author":"Buratti","year":"2015","journal-title":"Adv. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis","volume":"12","author":"Prasad","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1016\/j.jmb.2019.03.014","article-title":"Respiration Enhances TDP-43 Toxicity, but TDP-43 Retains Some Toxicity in the Absence of Respiration","volume":"431","author":"Park","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00401-018-1934-8","article-title":"Mitochondria, ER, and nuclear membrane defects reveal early mechanisms for upper motor neuron vulnerability with respect to TDP-43 pathology","volume":"137","author":"Gautam","year":"2019","journal-title":"Acta. Neuropathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/emboj.2011.471","article-title":"Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking","volume":"31","author":"Cohen","year":"2012","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1038\/ncomms6845","article-title":"An acetylation switch controls TDP-43 function and aggregation propensity","volume":"6","author":"Cohen","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/hmg\/ddt528","article-title":"Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models","volume":"23","author":"Cortez","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.neuroscience.2010.06.018","article-title":"Mutant TAR DNA-binding protein-43 induces oxidative injury in motor neuron-like cell","volume":"169","author":"Duan","year":"2010","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"gmr16029638","DOI":"10.4238\/gmr16029638","article-title":"Effects of mutant TDP-43 on the Nrf2\/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells","volume":"16","author":"Tian","year":"2017","journal-title":"Genet. Mol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.brainres.2016.03.036","article-title":"Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis","volume":"1647","author":"Shang","year":"2016","journal-title":"Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/humu.22319","article-title":"TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: Summary and update","volume":"34","author":"Lattante","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1038\/s41467-018-06111-6","article-title":"Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"134523","DOI":"10.1016\/j.neulet.2019.134523","article-title":"C9ORF72 protein function and immune dysregulation in amyotrophic lateral sclerosis","volume":"713","author":"Lai","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00401-013-1189-3","article-title":"Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins","volume":"126","author":"Mori","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-018-1921-0","article-title":"C9orf72-FTD\/ALS pathogenesis: Evidence from human neuropathological studies","volume":"137","author":"Vatsavayai","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40478-016-0316-5","article-title":"Gene-specific mitochondria dysfunctions in human TARDBP and C9ORF72 fibroblasts","volume":"4","author":"Onesto","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72-Related ALS\/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons","volume":"92","author":"Lu","year":"2016","journal-title":"Neuron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ebiom.2019.11.026","article-title":"Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity","volume":"50","author":"Birger","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10959","DOI":"10.1074\/jbc.M109.077560","article-title":"Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress granule assembly","volume":"285","author":"Emara","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15095","DOI":"10.1074\/jbc.RA119.008491","article-title":"Angiogenin activates the astrocytic Nrf2\/antioxidant-response element pathway and thereby protects murine neurons from oxidative stress","volume":"294","author":"Hoang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1002\/anie.201611446","article-title":"A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity","volume":"56","author":"Hoang","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fnins.2019.01310","article-title":"ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?","volume":"13","author":"Mejzini","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/ana.21993","article-title":"Paraoxonase gene mutations in amyotrophic lateral sclerosis","volume":"68","author":"Ticozzi","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1212\/WNL.0b013e3181a18674","article-title":"A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS","volume":"73","author":"Wills","year":"2009","journal-title":"Neurology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1845.e1","DOI":"10.1016\/j.neurobiolaging.2012.01.007","article-title":"Rare and common paraoxonase gene variants in amyotrophic lateral sclerosis patients","volume":"33","author":"Blokhuis","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S1474-4422(17)30401-5","article-title":"Novel genes associated with amyotrophic lateral sclerosis: Diagnostic and clinical implications","volume":"17","author":"Chia","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108525","DOI":"10.1016\/j.envres.2019.108525","article-title":"Residential exposure to ultra high frequency electromagnetic fields emitted by Global System for Mobile (GSM) antennas and amyotrophic lateral sclerosis incidence: A geo-epidemiological population-based study","volume":"176","author":"Luna","year":"2019","journal-title":"Environ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gunnarsson, L.G., and Bodin, L. (2018). Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses. Int. J. Environ. Res. Public. Health., 15.","DOI":"10.3390\/ijerph15112371"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Gunnarsson, L.G., and Bodin, L. (2019). Occupational Exposures and Neurodegenerative Diseases-A Systematic Literature Review and Meta-Analyses. Int. J. Environ. Res. Public. Health., 16.","DOI":"10.3390\/ijerph16030337"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/oemed-2016-103780","article-title":"Occupational exposure and amyotrophic lateral sclerosis in a prospective cohort","volume":"74","author":"Koeman","year":"2017","journal-title":"Occup. Environ. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Filippini, T., Tesauro, M., Fiore, M., Malagoli, C., Consonni, M., Violi, F., Iacuzio, L., Arcolin, E., Oliveri Conti, G., and Cristaldi, A. (2020). Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study. Int. J. Environ. Res. Public. Health., 17.","DOI":"10.3390\/ijerph17082882"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1212\/WNL.0000000000000952","article-title":"Residential exposure to extremely low frequency electromagnetic fields and the risk of ALS","volume":"83","author":"Seelen","year":"2014","journal-title":"Neurology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00484-020-01896-y","article-title":"The role of magnetic fields in neurodegenerative diseases","volume":"65","author":"Riancho","year":"2021","journal-title":"Int. J. Biometeorol."},{"key":"ref_73","first-page":"456","article-title":"Work related etiology of amyotrophic lateral sclerosis (ALS): A meta-analysis","volume":"26","author":"Capozzella","year":"2014","journal-title":"Ann. Ig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"683897","DOI":"10.1155\/2012\/683897","article-title":"Electromagnetic fields, oxidative stress, and neurodegeneration","volume":"2012","author":"Consales","year":"2012","journal-title":"Int. J. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3109\/17482960802320396","article-title":"Amyotrophic lateral sclerosis (ALS) and extremely-low frequency (ELF) magnetic fields: A study in the SOD-1 transgenic mouse model","volume":"10","author":"Taxile","year":"2009","journal-title":"Amyotroph. Lateral. Scler."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11939","DOI":"10.1038\/s41598-021-91349-2","article-title":"Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis: A dose-response meta-analysis","volume":"11","author":"Filippini","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1016\/j.biocel.2008.05.022","article-title":"Chronic exposure to 50 Hz magnetic fields causes a significant weakening of antioxidant defence systems in aged rat brain","volume":"40","author":"Falone","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.brainresbull.2005.09.011","article-title":"Effects of extremely low-frequency magnetic field in the brain of rats","volume":"68","year":"2006","journal-title":"Brain. Res. Bull."},{"key":"ref_79","first-page":"378278","article-title":"Dysregulation of iron metabolism in Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis","volume":"2011","author":"Oshiro","year":"2011","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1038\/srep08585","article-title":"Low-frequency magnetic fields do not aggravate disease in mouse models of Alzheimer\u2019s disease and amyotrophic lateral sclerosis","volume":"5","author":"Liebl","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ajim.22791","article-title":"Amyotrophic lateral sclerosis\u2014A case report and mechanistic review of the association with toluene and other volatile organic compounds","volume":"61","author":"Ratner","year":"2018","journal-title":"Am. J. Ind. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10654-020-00624-5","article-title":"A mixtures approach to solvent exposures and amyotrophic lateral sclerosis: A population-based study in Denmark","volume":"35","author":"Dickerson","year":"2020","journal-title":"Eur. J. Epidemiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/oemed-2016-103700","article-title":"Occupational exposures and the risk of amyotrophic lateral sclerosis","volume":"74","author":"Peters","year":"2017","journal-title":"Occup. Environ. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1289\/ehp.0900580","article-title":"Workplace exposures and the risk of amyotrophic lateral sclerosis","volume":"117","author":"Fang","year":"2009","journal-title":"Environ. Health. Perspect."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/jnnp-2015-310750","article-title":"Job-related formaldehyde exposure and ALS mortality in the USA","volume":"87","author":"Roberts","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/jnnp.2008.156976","article-title":"Prospective study of chemical exposures and amyotrophic lateral sclerosis","volume":"80","author":"Weisskopf","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.envres.2012.06.007","article-title":"Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: A meta-analysis of epidemiological studies: Pesticide exposure as a risk factor for ALS","volume":"117","author":"Malek","year":"2012","journal-title":"Environ. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1159\/000453359","article-title":"Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England","volume":"17","author":"Andrew","year":"2017","journal-title":"Neurodegener. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.envpol.2014.12.010","article-title":"Exposure to hazardous air pollutants and the risk of amyotrophic lateral sclerosis","volume":"197","author":"Malek","year":"2015","journal-title":"Environ. Pollut."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1007\/s00420-002-0344-2","article-title":"Possibilities to control the health risk of petrochemical workers","volume":"75","author":"Georgieva","year":"2002","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1007\/s11064-017-2248-2","article-title":"Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis","volume":"42","author":"Cheong","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1001\/jamaneurol.2013.234","article-title":"An imbalance between excitatory and inhibitory neurotransmitters in amyotrophic lateral sclerosis revealed by use of 3-T proton magnetic resonance spectroscopy","volume":"70","author":"Foerster","year":"2013","journal-title":"JAMA. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.neulet.2014.04.020","article-title":"Motor cortex glutathione deficit in ALS measured in vivo with the J-editing technique","volume":"570","author":"Weiduschat","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0006-2952(01)00652-9","article-title":"The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: The involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A","volume":"62","author":"Myhre","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/(SICI)1097-4598(199709)20:9<1137::AID-MUS7>3.0.CO;2-9","article-title":"Corticomotor threshold is reduced in early sporadic amyotrophic lateral sclerosis","volume":"20","author":"Mills","year":"1997","journal-title":"Muscle Nerve"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s004010050950","article-title":"Immunohistochemical analysis of spinal cord lesions in amyotrophic lateral sclerosis using microtubule-associated protein 2 (MAP2) antibodies","volume":"97","author":"Kikuchi","year":"1999","journal-title":"Acta Neuropathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1471-4159.2003.01505.x","article-title":"Altered levels and distribution of microtubule-associated proteins before disease onset in a mouse model of amyotrophic lateral sclerosis","volume":"84","author":"Farah","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.legalmed.2006.11.014","article-title":"Toluene inhalation induced neuronal damage in the spinal cord and changes of neurotrophic factors in rat","volume":"9","author":"Gotohda","year":"2007","journal-title":"Leg. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.chemosphere.2018.01.076","article-title":"Trace elements in ALS patients and their relationships with clinical severity","volume":"197","author":"Oggiano","year":"2018","journal-title":"Chemosphere"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ana.25932","article-title":"Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort","volume":"89","author":"Peters","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Parkin Kullmann, J.A., and Pamphlett, R. (2018). A Comparison of Mercury Exposure from Seafood Consumption and Dental Amalgam Fillings in People with and without Amyotrophic Lateral Sclerosis (ALS): An International Online Case-Control Study. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15122874"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1080\/21678421.2020.1753777","article-title":"Keratinous biomarker of mercury exposure associated with amyotrophic lateral sclerosis risk in a nationwide U.S. study","volume":"21","author":"Andrew","year":"2020","journal-title":"Amyotroph. Lateral. Scler. Frontotemporal. Degener."},{"key":"ref_103","first-page":"844","article-title":"Mercury in hair of patients with ALS","volume":"29","author":"Mano","year":"1989","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jns.2015.10.023","article-title":"Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study","volume":"359","author":"Bocca","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/0022-510X(93)90243-R","article-title":"Mercury and selenium contents in amyotrophic lateral sclerosis in Hokkaido, the northernmost island of Japan","volume":"118","author":"Moriwaka","year":"1993","journal-title":"J. Neurol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Dickerson, A.S., Hansen, J., Gredal, O., and Weisskopf, M.G. (2020). Study of Occupational Chromium, Iron, and Nickel Exposure and Amyotrophic Lateral Sclerosis in Denmark. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17218086"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuro.2016.06.015","article-title":"Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis","volume":"61","author":"Wang","year":"2017","journal-title":"Neurotoxicology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuro.2020.09.003","article-title":"Amyotrophic lateral sclerosis and lead: A systematic update","volume":"81","author":"Farace","year":"2020","journal-title":"Neurotoxicology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jtemb.2016.12.012","article-title":"Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study","volume":"43","author":"Vinceti","year":"2017","journal-title":"J. Trace. Elem. Med. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1289\/ehp.11193","article-title":"Association of lead exposure with survival in amyotrophic lateral sclerosis","volume":"116","author":"Kamel","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.nbd.2009.11.007","article-title":"Lead exposure stimulates VEGF expression in the spinal cord and extends survival in a mouse model of ALS","volume":"37","author":"Barbeito","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.neuro.2009.07.010","article-title":"The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis","volume":"30","author":"Johnson","year":"2009","journal-title":"Neurotoxicology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/toxsci\/kfy267","article-title":"Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology","volume":"167","author":"Ash","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"709","DOI":"10.5604\/17322693.1208036","article-title":"Misregulation of iron homeostasis in amyotrophic lateral sclerosis","volume":"70","author":"Gajowiak","year":"2016","journal-title":"Postepy. Hig. Med. Dosw."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"109820","DOI":"10.1016\/j.envres.2020.109820","article-title":"CSF neurotoxic metals\/metalloids levels in amyotrophic lateral sclerosis patients: Comparison between bulbar and spinal onset","volume":"188","author":"Patti","year":"2020","journal-title":"Environ. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"110292","DOI":"10.1016\/j.envres.2020.110292","article-title":"Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data","volume":"192","author":"Tesauro","year":"2021","journal-title":"Environ. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1017\/erm.2017.9","article-title":"Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis","volume":"19","author":"Aldanondo","year":"2017","journal-title":"Expert. Rev. Mol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12011-014-0060-2","article-title":"Selenoproteins in nervous system development and function","volume":"161","author":"Pitts","year":"2014","journal-title":"Biol. Trace. Elem. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.abb.2013.02.021","article-title":"Selenium homeostasis and antioxidant selenoproteins in brain: Implications for disorders in the central nervous system","volume":"536","author":"Steinbrenner","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.neuro.2012.04.019","article-title":"Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans","volume":"33","author":"Estevez","year":"2012","journal-title":"Neurotoxicology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/toxsci\/kfh149","article-title":"Induction and binding of Cd, Cu, and Zn to metallothionein in carp (Cyprinus carpio) using HPLC-ICP-TOFMS","volume":"80","author":"Infante","year":"2004","journal-title":"Toxicol. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10072-020-04957-7","article-title":"An overview on amyotrophic lateral sclerosis and cadmium","volume":"42","author":"Oggiano","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.biopha.2016.07.035","article-title":"Multifaceted effects of aluminium in neurodegenerative diseases: A review","volume":"83","author":"Maya","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0022-510X(90)90266-P","article-title":"Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy","volume":"98","author":"Kihira","year":"1990","journal-title":"J. Neurol. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1007\/s12011-020-02501-4","article-title":"Amyotrophic Lateral Sclerosis After Exposure to Manganese from Traditional Medicine Procedures in Kenya","volume":"199","author":"Roos","year":"2021","journal-title":"Biol. Trace. Elem. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12940-017-0297-2","article-title":"Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis","volume":"16","author":"Vinceti","year":"2017","journal-title":"Environ. Health"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1136\/jnnp.57.7.810","article-title":"October 1942: A strange epidemic paralysis in Saval, Verona, Italy. Revision and diagnosis 50 years later of tri-ortho-cresyl phosphate poisoning","volume":"57","author":"Tosi","year":"1994","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1136\/oem.58.1.24","article-title":"Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945\u201394: An update","volume":"58","author":"Burns","year":"2001","journal-title":"Occup. Environ. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.envres.2017.02.025","article-title":"Pesticides, polychlorinated biphenyls and polycyclic aromatic hydrocarbons in cerebrospinal fluid of amyotrophic lateral sclerosis patients: A case-control study","volume":"155","author":"Vinceti","year":"2017","journal-title":"Environ. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tox.2018.07.014","article-title":"The link of organophosphorus pesticides with neurodegenerative and neurodevelopmental diseases based on evidence and mechanisms","volume":"409","author":"Mostafalou","year":"2018","journal-title":"Toxicology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tox.2015.07.004","article-title":"Acute and long-term exposure to chlorpyrifos induces cell death of basal forebrain cholinergic neurons through AChE variants alteration","volume":"336","author":"Moyano","year":"2015","journal-title":"Toxicology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1515\/aiht-2017-68-2989","article-title":"Adverse effects of organophosphorus pesticides on the liver: A brief summary of four decades of research","volume":"68","author":"Ahmadipour","year":"2017","journal-title":"Arh. Hig. Rada. Toksikol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/med.21528","article-title":"Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs","volume":"39","author":"Jaiswal","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_134","first-page":"CD001447","article-title":"Riluzole for amyotrophic lateral sclerosis (ALS)\/motor neuron disease (MND)","volume":"1","author":"Miller","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1474-4422(18)30054-1","article-title":"Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: A retrospective analysis of data from a dose-ranging study","volume":"17","author":"Fang","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3109\/21678421.2014.959024","article-title":"Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients","volume":"15","author":"Abe","year":"2014","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Writing Group on Behalf of the Edaravone (MCI-186) ALS 17 Study Group (2017). Exploratory double-blind, parallel-group, placebo-controlled extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener., 18, 20\u201331.","DOI":"10.1080\/21678421.2017.1362000"},{"key":"ref_138","unstructured":"Writing Group, and Edaravone (MCI-186) ALS 19 Study Group (2017). Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial. Lancet Neurol., 16, 505\u2013512."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/21678421.2017.1361442","article-title":"Post-hoc analysis of MCI186\u201317, the extension study to MCI186\u201316, the confirmatory double-blind, parallel-group, placebo-controlled study of edaravone in amyotrophic lateral sclerosis","volume":"18","author":"Takahashi","year":"2017","journal-title":"Amyotroph. Lateral. Scler. Frontotemporal Degener."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuint.2015.07.024","article-title":"Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress","volume":"90","author":"Jami","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Ahmadinejad, F., Geir M\u00f8ller, S., Hashemzadeh-Chaleshtori, M., Bidkhori, G., and Jami, M.-S. (2017). Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress. Antioxidants., 6.","DOI":"10.3390\/antiox6030051"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1021\/jp110400t","article-title":"OH radical scavenging activity of Edaravone: Mechanism and kinetics","volume":"115","author":"Galano","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.phrs.2015.03.021","article-title":"Controlled and Impaired Mitochondrial Quality in Neurons: Molecular Physiology and Prospective Pharmacology","volume":"99","author":"Matic","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.freeradbiomed.2014.02.019","article-title":"Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis","volume":"70","author":"Miquel","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_145","first-page":"S683","article-title":"Coenzyme Q10 effects in neurological diseases","volume":"70","year":"2021","journal-title":"Physiol. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"415078","DOI":"10.1155\/2013\/415078","article-title":"Sulforaphane as a potential protective phytochemical against neurodegenerative diseases","volume":"2013","author":"Tarozzi","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s11357-019-00061-7","article-title":"Sulforaphane\u2014Role in aging and neurodegeneration","volume":"41","author":"Chondrogianni","year":"2019","journal-title":"Geroscience"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.chembiol.2014.09.019","article-title":"PMI: A \u0394\u03a8m independent pharmacological regulator of mitophagy","volume":"21","author":"East","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/15548627.2019.1644076","article-title":"ALS-FTLD-linked mutations of SQSTM1\/p62 disrupt selective autophagy and NFE2L2\/NRF2 anti-oxidative stress pathway","volume":"16","author":"Deng","year":"2020","journal-title":"Autophagy"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2016.01.020","article-title":"Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD","volume":"89","author":"Williams","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"19392","DOI":"10.1038\/s41598-021-98317-w","article-title":"CuATSM improves motor function and extends survival but is not tolerated at a high dose in SOD1G93A mice with a C57BL\/6 background","volume":"11","author":"Lum","year":"2021","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:12:09Z","timestamp":1760141529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,19]]},"references-count":151,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23169339"],"URL":"https:\/\/doi.org\/10.3390\/ijms23169339","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,19]]}}}