{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:33:08Z","timestamp":1793305988159,"version":"4.5.0"},"reference-count":96,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuropharmacology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.neuropharm.2020.108380","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T09:24:26Z","timestamp":1604309066000},"page":"108380","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":54,"special_numbering":"C","title":["Tetramethylpyrazine nitrone improves motor dysfunction and pathological manifestations by activating the PGC-1\u03b1\/Nrf2\/HO-1 pathway in ALS mice"],"prefix":"10.1016","volume":"182","author":[{"given":"Jing","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyou","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangwen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangmiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuropharm.2020.108380_bib1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0022-510X(00)00317-8","article-title":"Increased reactive oxygen species in familial amyotrophic lateral sclerosis with mutations in SOD1","volume":"176","author":"Ahmed","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib2","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1046\/j.1471-4159.1999.0722415.x","article-title":"Inducible nitric oxide synthase up\u2010regulation in a transgenic mouse model of familial amyotrophic lateral sclerosis","volume":"72","author":"Almer","year":"1999","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.freeradbiomed.2009.11.018","article-title":"Oxidative stress in ALS: key role in motor neuron injury and therapeutic target","volume":"48","author":"Barber","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib4","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 (BBA) - Mol. Basis Dis."},{"key":"10.1016\/j.neuropharm.2020.108380_bib5","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/ana.410420416","article-title":"Increased 3\u2010nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis","volume":"42","author":"Beal","year":"1997","journal-title":"Ann. Neurol.: Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJM199403033300901","article-title":"A controlled trial of riluzole in amyotrophic lateral sclerosis","volume":"330","author":"Bensimon","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1017\/cjn.2016.284","article-title":"Panel of oxidative stress and inflammatory biomarkers in ALS: a pilot study","volume":"44","author":"Blasco","year":"2017","journal-title":"Can. J. Neurol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib8","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/nn.2660","article-title":"Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS","volume":"13","author":"Bosco","year":"2010","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neulet.2016.04.065","article-title":"Oxidative stress and mitochondrial damage in the pathogenesis of ALS: new perspectives","volume":"636","author":"Bozzo","year":"2017","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuropharm.2020.108380_bib10","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1365-2990.1996.tb00907.x","article-title":"Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease","volume":"22","author":"Bruijn","year":"1996","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0361-9230(03)00179-5","article-title":"Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals","volume":"61","author":"Carr\u0131\u0300","year":"2003","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.neuropharm.2020.108380_bib12","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.2174\/092986710791163939","article-title":"Riluzole, neuroprotection and amyotrophic lateral sclerosis","volume":"17","author":"Cheah","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib13","first-page":"406","article-title":"Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal","volume":"186","author":"Cheeseman","year":"1994","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/146608202760196048","article-title":"Cu\/Zn superoxide dismutase (SOD1) mutations associated with familial amyotrophic lateral sclerosis (ALS) affect cellular free radical release in the presence of oxidative stress","volume":"3","author":"Cookson","year":"2002","journal-title":"Amyotroph Lateral Scler."},{"key":"10.1016\/j.neuropharm.2020.108380_bib15","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.cmet.2012.03.019","article-title":"Elevated PGC-1\u03b1 activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS","volume":"15","author":"Da Cruz","year":"2012","journal-title":"Cell Metabol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib16","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1468-1331.2011.03501.x","article-title":"EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)\u2013revised report of an EFNS task force","volume":"19","author":"Diagnosis","year":"2012","journal-title":"Eur. J. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2014.06.010","article-title":"Metformin induces microRNA-34a to downregulate the Sirt1\/Pgc-1\u03b1\/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents","volume":"74","author":"Do","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib18","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":"D'Amico","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib19","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1093\/hmg\/ddt202","article-title":"PGC-1\u03b1 is a male-specific disease modifier of human and experimental amyotrophic lateral sclerosis","volume":"22","author":"Eschbach","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuropharm.2020.108380_bib20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0197-4580(02)00078-7","article-title":"A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes","volume":"23","author":"Esposito","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neuropharm.2020.108380_bib21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0076-6879(90)86134-H","article-title":"[42] Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal","author":"Esterbauer","year":"1990","journal-title":"Methods Enzymol"},{"key":"10.1016\/j.neuropharm.2020.108380_bib22","first-page":"1760","article-title":"Therapeutic effects of dl-3-n-butylphthalide in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"125","author":"Feng","year":"2012","journal-title":"Chin. Med. J."},{"key":"10.1016\/j.neuropharm.2020.108380_bib23","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrneurol.2011.152","article-title":"Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis","volume":"7","author":"Ferraiuolo","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib24","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1046\/j.1471-4159.1997.69052064.x","article-title":"Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis","volume":"69","author":"Ferrante","year":"1997","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib25","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00401-011-0805-3","article-title":"Glial nuclear aggregates of superoxide dismutase-1 are regularly present in patients with amyotrophic lateral sclerosis","volume":"121","author":"Forsberg","year":"2011","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib26","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12017-018-8478-x","article-title":"Neuroprotective effect and mechanism of action of tetramethylpyrazine nitrone for ischemic stroke therapy","volume":"20","author":"G","year":"2018","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib27","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/bph.14102","article-title":"Tetramethylpyrazine nitrone activates the BDNF\/Akt\/CREB pathway to promote post-ischaemic neuroregeneration and recovery of neurological functions in rats","volume":"175","author":"G","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib28","first-page":"453","article-title":"Malondialdehyde (MDA) as a lipid peroxidation marker","volume":"57","author":"Gawe\u0142","year":"2004","journal-title":"Wiad. Lek."},{"key":"10.1016\/j.neuropharm.2020.108380_bib29","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1136\/thorax.57.9.765","article-title":"\u03b2-Actin and GAPDH housekeeping gene expression in asthmatic airways is variable and not suitable for normalising mRNA levels","volume":"57","author":"Glare","year":"2002","journal-title":"Thorax"},{"key":"10.1016\/j.neuropharm.2020.108380_bib30","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s00204-014-1302-y","article-title":"Tetramethylpyrazine (TMP) protects against sodium arsenite-induced nephrotoxicity by suppressing ROS production, mitochondrial dysfunction, pro-inflammatory signaling pathways and programed cell death","volume":"89","author":"Gong","year":"2015","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.brainres.2005.12.035","article-title":"Brain penetration of the novel free radical trapping neuroprotectant NXY-059 in rats subjected to permanent focal ischemia","volume":"1072","author":"Green","year":"2006","journal-title":"Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib32","doi-asserted-by":"crossref","first-page":"12524","DOI":"10.1073\/pnas.0705044104","article-title":"Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis","volume":"104","author":"Gruzman","year":"2007","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.neuropharm.2020.108380_bib33","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1073\/pnas.1115402109","article-title":"An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1","volume":"109","author":"Guareschi","year":"2012","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.neuropharm.2020.108380_bib34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3858\/emm.2009.41.3.017","article-title":"Sensory involvement in the SOD1-G93A mouse model of amyotrophic lateral sclerosis","volume":"41","author":"Guo","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib35","article-title":"Therapeutic effects of multifunctional tetramethylpyrazine nitrone on models of Parkinson's disease in vitro and in vivo","volume":"b13\u2013","author":"Guo","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.neuropharm.2020.108380_bib36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/ana.410390203","article-title":"Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis","volume":"39","author":"Gurney","year":"1996","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1212\/WNL.50.1.62","article-title":"Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis","volume":"50","author":"Gurney","year":"1998","journal-title":"Neurology"},{"key":"10.1016\/j.neuropharm.2020.108380_bib38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#","article-title":"Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS","volume":"23","author":"Hall","year":"1998","journal-title":"Glia"},{"key":"10.1016\/j.neuropharm.2020.108380_bib39","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1093\/hmg\/ddn131","article-title":"Molecular dissection of ALS-associated toxicity of SOD1 in transgenic mice using an exon-fusion approach","volume":"17","author":"Han-Xiang","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuropharm.2020.108380_bib40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1179\/016164105X18430","article-title":"Oxidative stress and metal content in blood and cerebrospinal fluid of amyotrophic lateral sclerosis patients with and without a Cu, Zn-superoxide dismutase mutation","volume":"27","author":"Ihara","year":"2005","journal-title":"Neurol. Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib41","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.expneurol.2008.07.017","article-title":"Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice","volume":"213","author":"Ito","year":"2008","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib42","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ana.21319","article-title":"Oxidized\/misfolded superoxide dismutase\u20101: the cause of all amyotrophic lateral sclerosis?","volume":"62","author":"Kabashi","year":"2007","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00401-005-1019-3","article-title":"Redox system expression in the motor neurons in amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models","volume":"110","author":"Kato","year":"2005","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0022-510X(00)00423-8","article-title":"Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuronopathy (pmn)","volume":"180","author":"Kennel","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib45","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.neuropharm.2020.108380_bib46","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/jnen\/62.1.88","article-title":"PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients","volume":"62","author":"Kim","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib47","first-page":"537","article-title":"Neuroinflammation in motor neuron disease","volume":"77","author":"Komine","year":"2015","journal-title":"Nagoya J. Med. Sci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib48","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.expneurol.2007.05.026","article-title":"Activation of the Nrf2\u2013ARE 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":"10.1016\/j.neuropharm.2020.108380_bib49","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/mus.22217","article-title":"PGC\u20101\u03b1 protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model","volume":"44","author":"Liang","year":"2011","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.neuropharm.2020.108380_bib50","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metabol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib51","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/WCO.0000000000000730","article-title":"Epidemiology of amyotrophic lateral sclerosis: an update of recent literature","volume":"32","author":"Longinetti","year":"2019","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib52","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":"Lopez-Gonzalez","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.neuropharm.2020.108380_bib53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/jnc.13970","article-title":"Tetramethylpyrazine nitrone protects retinal ganglion cells against N-methyl-d-aspartate-induced excitotoxicity","volume":"141","author":"Luo","year":"2017","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib54","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.15585\/mmwr.mm6746a1","article-title":"Prevalence of amyotrophic lateral sclerosis\u2014United States, 2015","volume":"67","author":"Mehta","year":"2018","journal-title":"MMWR (Morb. Mortal. Wkly. Rep.)"},{"key":"10.1016\/j.neuropharm.2020.108380_bib55","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/836760","article-title":"SOD1 and DJ-1 converge at Nrf2 pathway: a clue for antioxidant therapeutic potential in neurodegeneration","volume":"2013","author":"Milani","year":"2013","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.neuropharm.2020.108380_bib56","article-title":"Riluzole for amyotrophic lateral sclerosis (ALS)\/motor neuron disease (MND)","volume":"3","author":"Miller","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.neuropharm.2020.108380_bib57","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1016\/S0140-6736(07)60944-1","article-title":"Amyotrophic lateral sclerosis","volume":"369","author":"Mitchell","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.neuropharm.2020.108380_bib58","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fnins.2014.00252","article-title":"ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease","volume":"8","author":"Moloney","year":"2014","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib59","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1093\/hmg\/ddx093","article-title":"TDP-43 mutations causing amyotrophic lateral sclerosis are associated with altered expression of RNA-binding protein hnRNP K and affect the Nrf2 antioxidant pathway","volume":"26","author":"Moujalled","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.neuropharm.2020.108380_bib60","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.freeradbiomed.2011.03.027","article-title":"Neuroprotective effect of Nrf2\/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis","volume":"51","author":"Neymotin","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib61","first-page":"281","article-title":"Malondialdehyde determination as index of lipid peroxidation","volume":"3","author":"Odukoya","year":"1994","journal-title":"Int. J. Biochem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib62","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/jnr.24368","article-title":"Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis","volume":"97","author":"Ohta","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib63","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1023\/A:1027384432715","article-title":"Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amiotrophic lateral sclerosis patients","volume":"22","author":"Oteiza","year":"1997","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib64","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/21678421.2019.1599955","article-title":"Post-hoc analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis","volume":"20","author":"Palumbo","year":"2019","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"10.1016\/j.neuropharm.2020.108380_bib65","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/ana.410440518","article-title":"Protein modification by the lipid peroxidation product 4\u2010hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients","volume":"44","author":"Pedersen","year":"1998","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib66","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/878030","article-title":"Nrf2\/ARE signaling pathway: key mediator in oxidative stress and potential therapeutic target in ALS","volume":"2012","author":"Petri","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"10.1016\/j.neuropharm.2020.108380_bib67","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/525097","article-title":"Blood biomarkers for amyotrophic lateral sclerosis: myth or reality?","volume":"2014","author":"Robelin","year":"2014","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.neuropharm.2020.108380_bib68","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.neuropharm.2020.108380_bib69","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic lateral sclerosis","volume":"344","author":"Rowland","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib70","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/mus.26740","article-title":"Long\u2010term edaravone efficacy in amyotrophic lateral sclerosis: post\u2010hoc analyses of Study 19 (MCI186\u201019","volume":"61","author":"Shefner","year":"2020","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.neuropharm.2020.108380_bib71","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0024-3205(00)00686-X","article-title":"The antiplatelet activity of tetramethylpyrazine is mediated through activation of NO synthase","volume":"67","author":"Sheu","year":"2000","journal-title":"Life Sci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib72","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF02981969","article-title":"Antithrombotic effects of tetramethylpyrazine in in vivo experiments","volume":"73","author":"Sheu","year":"2001","journal-title":"Int. J. Hematol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib73","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators","volume":"127","author":"St-Pierre","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.neuropharm.2020.108380_bib74","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1002\/jnr.23034","article-title":"Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models","volume":"90","author":"Sun","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib75","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1136\/jnnp.2009.181719","article-title":"The human G93A SOD1 phenotype closely resembles sporadic amyotrophic lateral sclerosis","volume":"81","author":"Synofzik","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.neuropharm.2020.108380_bib76","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuropharm.2017.03.022","article-title":"Neuroprotective and axonal outgrowth-promoting effects of tetramethylpyrazine nitrone in chronic cerebral hypoperfusion rats and primary hippocampal neurons exposed to hypoxia","volume":"118","author":"T","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuropharm.2020.108380_bib77","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/ana.410180402","article-title":"Amyotrophic leteral sclerosis: part 2. Etiopathogenesis","volume":"18","author":"Tandan","year":"1985","journal-title":"Ann. Neurol.: Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib78","doi-asserted-by":"crossref","first-page":"13574","DOI":"10.1523\/JNEUROSCI.4099-08.2008","article-title":"Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis","volume":"28","author":"Vargas","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108380_bib79","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13024-015-0036-5","article-title":"Cytoplasmic mislocalization of RNA splicing factors and aberrant neuronal gene splicing in TDP-43 transgenic pig brain","volume":"10","author":"Wang","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuropharm.2020.108380_bib80","first-page":"17","article-title":"How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis?","author":"Watanabe","year":"2018","journal-title":"J. Clin. Biochem. Nutr."},{"key":"10.1016\/j.neuropharm.2020.108380_bib81","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.mito.2013.01.006","article-title":"Regulation of mitochondrial biogenesis and PGC-1\u03b1 under cellular stress","volume":"13","author":"Wenz","year":"2013","journal-title":"Mitochondrion"},{"key":"10.1016\/j.neuropharm.2020.108380_bib82","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/S0306-4522(99)00512-6","article-title":"Repeated stimuli for axonal growth causes motoneuron death in adult rats: the effect of botulinum toxin followed by partial denervation","volume":"95","author":"White","year":"1999","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108380_bib83","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s12017-019-08543-9","article-title":"Tetramethylpyrazine nitrone reduces oxidative stress to alleviate cerebral vasospasm in experimental subarachnoid hemorrhage models","volume":"21","author":"Wu","year":"2019","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib84","doi-asserted-by":"crossref","first-page":"37148","DOI":"10.1038\/srep37148","article-title":"Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy","volume":"6","author":"Z","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuropharm.2020.108380_bib85","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1471-4159.2011.07177.x","article-title":"Misfolded superoxide dismutase\u20101 in CSF from amyotrophic lateral sclerosis patients","volume":"117","author":"Zetterstr\u00f6m","year":"2011","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuropharm.2020.108380_bib86","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1007\/s11064-016-2013-y","article-title":"Tetramethylpyrazine nitrone improves neurobehavioral functions and confers neuroprotection on rats with traumatic brain injury","volume":"41","author":"Zhang","year":"2016","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.neuropharm.2020.108380_bib87","doi-asserted-by":"crossref","first-page":"37148","DOI":"10.1038\/srep37148","article-title":"Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuropharm.2020.108380_bib88","doi-asserted-by":"crossref","first-page":"37148","DOI":"10.1038\/srep37148","article-title":"Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.neuropharm.2020.108380_bib89","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuropharm.2017.03.022","article-title":"Neuroprotective and axonal outgrowth-promoting effects of tetramethylpyrazine nitrone in chronic cerebral hypoperfusion rats and primary hippocampal neurons exposed to hypoxia","volume":"118","author":"Zhang","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuropharm.2020.108380_bib90","article-title":"A novel danshensu-tetramethylpyrazine conjugate DT-010 provides cardioprotection through the PGC-1\u03b1\/Nrf2\/HO-1 pathway","volume":"b17\u201300313","author":"Zhang","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.neuropharm.2020.108380_bib91","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/bph.14102","article-title":"Tetramethylpyrazine nitrone activates the BDNF\/Akt\/CREB pathway to promote post-ischaemic neuroregeneration and recovery of neurological functions in rats","volume":"175","author":"Zhang","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108380_bib92","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12017-018-8478-x","article-title":"Neuroprotective effect and mechanism of action of tetramethylpyrazine nitrone for ischemic stroke therapy","volume":"20","author":"Zhang","year":"2018","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib93","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12017-018-8478-x","article-title":"Neuroprotective effect and mechanism of action of tetramethylpyrazine nitrone for ischemic stroke therapy","volume":"20","author":"Zhang","year":"2018","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.neuropharm.2020.108380_bib94","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1750-1326-6-51","article-title":"Peroxisome proliferator activator receptor gamma coactivator-1 alpha (PGC-1\u03b1) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis","volume":"6","author":"Zhao","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuropharm.2020.108380_bib95","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1161\/01.STR.0000252090.44428.82","article-title":"Clinical trials of neuroprotective therapies","volume":"38","author":"Zivin","year":"2007","journal-title":"Stroke"},{"key":"10.1016\/j.neuropharm.2020.108380_bib96","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jnnp-2016-315018","article-title":"Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis","volume":"88","author":"Zou","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"}],"container-title":["Neuropharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820304482?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820304482?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T07:06:41Z","timestamp":1758438401000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0028390820304482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":96,"alternative-id":["S0028390820304482"],"URL":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108380","relation":{},"ISSN":["0028-3908"],"issn-type":[{"value":"0028-3908","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tetramethylpyrazine nitrone improves motor dysfunction and pathological manifestations by activating the PGC-1\u03b1\/Nrf2\/HO-1 pathway in ALS mice","name":"articletitle","label":"Article Title"},{"value":"Neuropharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108380","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108380"}}