{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:32:20Z","timestamp":1780561940574,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82150107"],"award-info":[{"award-number":["82150107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["XDB39050600"],"award-info":[{"award-number":["XDB39050600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Priority Research Program of Chinese Academy of Sciences","award":["82150107"],"award-info":[{"award-number":["82150107"]}]},{"name":"Strategic Priority Research Program of Chinese Academy of Sciences","award":["XDB39050600"],"award-info":[{"award-number":["XDB39050600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, with limited effective treatments. Recently, the exploration of natural products has unveiled their potential in exerting neuroprotective effects, offering a promising avenue for ALS therapy. In this study, the therapeutic effects of rutin, a natural flavonoid glycoside with neuroprotective properties, were evaluated in a superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. We showed that rutin reduced the level of SOD1 aggregation and diminished glial cell activation in spinal cords and brainstems, resulting in significantly improved motor function and motor neuron restoration in SOD1-G93A mice. Our findings indicated that rutin\u2019s multi-targeted approach to SOD1-related pathology makes it a promising candidate for the treatment of ALS.<\/jats:p>","DOI":"10.3390\/ijms251910392","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T03:44:13Z","timestamp":1727408653000},"page":"10392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rutin Ameliorates ALS Pathology by Reducing SOD1 Aggregation and Neuroinflammation in an SOD1-G93A Mouse Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Xiaoyu","family":"Du","sequence":"first","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanxiu","family":"Dong","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjie","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-4765","authenticated-orcid":false,"given":"Ruitian","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrneurol.2011.150","article-title":"Clinical genetics of amyotrophic lateral sclerosis: What do we really know?","volume":"7","author":"Andersen","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/364362c0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"364","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"De La Cruz, E., Esselin, F., Polge, A., Mouzat, K., and Guissart, C. (2024). Most SOD1 mutations are pathogenic, and their identification can lead to early access to treatment. J. Neurol. Neurosurg. Psychiatry.","DOI":"10.1136\/jnnp-2024-333939"},{"key":"ref_5","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":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13024-016-0145-9","article-title":"Immunochemical characterization on pathological oligomers of mutant Cu\/Zn-superoxide dismutase in amyotrophic lateral sclerosis","volume":"12","author":"Tokuda","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1073\/pnas.1516725113","article-title":"Nonnative SOD1 trimer is toxic to motor neurons in a model of amyotrophic lateral sclerosis","volume":"113","author":"Proctor","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S1474-4422(17)30163-1","article-title":"Edaravone: A new treatment for ALS on the horizon?","volume":"16","author":"Hardiman","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJMoa2003715","article-title":"Phase 1\u20132 trial of antisense oligonucleotide tofersen for SOD1 ALS","volume":"383","author":"Miller","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1474-4422(18)30091-7","article-title":"Riluzole, disease stage and survival in ALS","volume":"17","author":"Dharmadasa","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMoa1916945","article-title":"Trial of Sodium Phenylbutyrate\u2013Taurursodiol for Amyotrophic Lateral Sclerosis","volume":"383","author":"Paganoni","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/ptr.6904","article-title":"Therapeutic benefits of rutin and its nanoformulations","volume":"35","author":"Negahdari","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.2174\/0929867324666171003114154","article-title":"Rutin as neuroprotective agent: From bench to bedside","volume":"26","author":"Budzynska","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bbr.2014.02.002","article-title":"Rutin improves spatial memory in Alzheimer\u2019s disease transgenic mice by reducing A\u03b2 oligomer level and attenuating oxidative stress and neuroinflammation","volume":"264","author":"Xu","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.neuroscience.2012.02.046","article-title":"Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type","volume":"210","author":"Javed","year":"2012","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaau6328","DOI":"10.1126\/sciadv.aau6328","article-title":"Sodium rutin ameliorates Alzheimer\u2019s disease\u2013like pathology by enhancing microglial amyloid-\u03b2 clearance","volume":"5","author":"Pan","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12640-011-9295-2","article-title":"Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson\u2019s disease","volume":"22","author":"Khan","year":"2012","journal-title":"Neurotox. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3892\/ijmm.2013.1375","article-title":"Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity","volume":"32","author":"Magalingam","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1080\/1028415X.2021.1956254","article-title":"Neuroprotective effects of rutin on ASH neurons in Caenorhabditis elegans model of Huntington\u2019s disease","volume":"25","author":"Cordeiro","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111323","DOI":"10.1016\/j.fct.2020.111323","article-title":"Rutin protects Huntington\u2019s disease through the insulin\/IGF1 (IIS) signaling pathway and autophagy activity: Study in Caenorhabditis elegans model","volume":"141","author":"Cordeiro","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","unstructured":"Martin, C.R., Patel, V.B., and Preedy, V.R. (2023). Chapter 8\u2014Rutin and Its Application to Amyotrophic Lateral Sclerosis, in Treatments, Nutraceuticals, Supplements, and Herbal Medicine in Neurological Disorders, Academic Press."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e8611","DOI":"10.1002\/rcm.8611","article-title":"The effects of rutin and troxerutin on stabilizing SOD1 and inhibiting protein aggregation","volume":"34","author":"Zhuang","year":"2020","journal-title":"Rapid Commun. Mass Spectrom. RCM"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.neuro.2012.03.003","article-title":"Rutin inhibits \u03b2-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines","volume":"33","author":"Wang","year":"2012","journal-title":"NeuroToxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12974-021-02182-3","article-title":"Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer\u2019s disease","volume":"18","author":"Sun","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2023). Molecular investigations of protein aggregation in the pathogenesis of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010704"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S1474-4422(11)70015-1","article-title":"Neuroinflammation in amyotrophic lateral sclerosis: Role of glial activation in motor neuron disease","volume":"10","author":"Philips","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gene.2015.11.049","article-title":"Mutant SOD1 mediated pathogenesis of Amyotrophic Lateral Sclerosis","volume":"577","author":"Kaur","year":"2016","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1021\/acs.jafc.1c06918","article-title":"Inhibition of islet amyloid polypeptide fibrillation by structurally diverse phenolic compounds and fibril disaggregation potential of Rutin and Quercetin","volume":"70","author":"Abioye","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jss.2016.02.041","article-title":"Rutin attenuates neuroinflammation in spinal cord injury rats","volume":"203","author":"Wu","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1007\/s11064-016-1863-7","article-title":"Rutin inhibits neuroinflammation and provides neuroprotection in an experimental rat model of subarachnoid hemorrhage, possibly through suppressing the RAGE\u2013NF-\u03baB inflammatory signaling pathway","volume":"41","author":"Hao","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1007\/s12035-021-02387-w","article-title":"Sirtuin acetylation and deacetylation: A complex paradigm in neurodegenerative disease","volume":"58","author":"Khan","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/13813455.2017.1374978","article-title":"Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: Role of PI3K\/AKT\/GSK-3\u03b2\/NRF-2 signalling pathway","volume":"124","author":"Thabet","year":"2018","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1046\/j.1471-4159.2003.01652.x","article-title":"Interaction between flavonoids and the blood\u2013brain barrier: In vitro studies","volume":"85","author":"Youdim","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ijbiomac.2016.06.001","article-title":"Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia","volume":"91","author":"Ahmad","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1080\/17482960801984358","article-title":"Gender difference in levels of Cu\/Zn superoxide dismutase (SOD1) in cerebrospinal fluid of patients with amyotrophic lateral sclerosis","volume":"9","author":"Frutiger","year":"2008","journal-title":"Amyotroph. Lateral Scler."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:04:29Z","timestamp":1760112269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":36,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910392"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910392","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]}}}