{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:18:50Z","timestamp":1791901130544,"version":"4.3.4"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T00:00:00Z","timestamp":1570579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008714","name":"Motor Neurone Disease Research Institute of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008714","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1082271"],"award-info":[{"award-number":["APP1082271"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1084144"],"award-info":[{"award-number":["APP1084144"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1086786"],"award-info":[{"award-number":["APP1086786"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1105420"],"award-info":[{"award-number":["APP1105420"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microglial NLRP3 inflammasome activation is emerging as a key contributor to neuroinflammation during neurodegeneration. Pathogenic protein aggregates such as \u03b2\u2010amyloid and \u03b1\u2010synuclein trigger microglial NLRP3 activation, leading to caspase\u20101 activation and IL\u20101\u03b2 secretion. Both caspase\u20101 and IL\u20101\u03b2 contribute to disease progression in the mouse SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    model of amyotrophic lateral sclerosis (ALS), suggesting a role for microglial NLRP3. Prior studies, however, suggested SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mice microglia do not express NLRP3, and SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    protein generated IL\u20101\u03b2 in microglia independent to NLRP3. Here, we demonstrate using\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    \u2010GFP gene knock\u2010in mice that microglia express NLRP3 in SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mice. We show that both aggregated and soluble SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    activates inflammasome in primary mouse microglia leading caspase\u20101 and IL\u20101\u03b2 cleavage, ASC speck formation, and the secretion of IL\u20101\u03b2 in a dose\u2010 and time\u2010dependent manner. Importantly, SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    was unable to induce IL\u20101\u03b2 secretion from microglia deficient for\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    , or pretreated with the specific NLRP3 inhibitor MCC950, confirming NLRP3 as the key inflammasome complex mediating SOD1\u2010induced microglial IL\u20101\u03b2 secretion. Microglial NLRP3 upregulation was also observed in the TDP\u201043\n                    <jats:sup>Q331K<\/jats:sup>\n                    ALS mouse model, and TDP\u201043 wild\u2010type and mutant proteins could also activate microglial inflammasomes in a NLRP3\u2010dependent manner. Mechanistically, we identified the generation of reactive oxygen species and ATP as key events required for SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    \u2010mediated NLRP3 activation. Taken together, our data demonstrate that ALS microglia express NLRP3, and that pathological ALS proteins activate the microglial NLRP3 inflammasome. NLRP3 inhibition may therefore be a potential therapeutic approach to arrest microglial neuroinflammation and ALS disease progression.\n                  <\/jats:p>","DOI":"10.1002\/glia.23728","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T09:41:27Z","timestamp":1570614087000},"page":"407-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":220,"title":["The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins"],"prefix":"10.1002","volume":"68","author":[{"given":"Vandana","family":"Deora","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-7396","authenticated-orcid":false,"given":"John D.","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The University of Queensland  St. Lucia Queensland Australia"},{"name":"University of Queensland Centre for Clinical Research, Faculty of Medicine The University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo A.","family":"Albornoz","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The University of Queensland  St. Lucia Queensland Australia"},{"name":"Institute for Molecular Bioscience, and Centre for Inflammation and Disease Research The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"McAlary","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, Faculty of Science, Medicine and Health University of Wollongong  Wollongong New South Wales Australia"},{"name":"Illawarra Health and Medical Institute University of Wollongong  Wollongong New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril J.","family":"Jagaraj","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Centre for MND Research Macquarie University  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avril A. B.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, and Centre for Inflammation and Disease Research The University of Queensland  St. Lucia Queensland Australia"},{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie D.","family":"Atkin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Centre for MND Research Macquarie University  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, and Centre for Inflammation and Disease Research The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Schroder","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, and Centre for Inflammation and Disease Research The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin J.","family":"Yerbury","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, Faculty of Science, Medicine and Health University of Wollongong  Wollongong New South Wales Australia"},{"name":"Illawarra Health and Medical Institute University of Wollongong  Wollongong New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gordon","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The University of Queensland  St. Lucia Queensland Australia"},{"name":"University of Queensland Centre for 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