{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:57:01Z","timestamp":1792159021437,"version":"4.4.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,7,20]]},"abstract":"\n ALS is a fatal motor neuron disease of adult onset. Neuroinflammation contributes to ALS disease progression; however, the inflammatory trigger remains unclear. We report that ALS\u2013linked mutant superoxide dismutase 1 (SOD1) activates caspase-1 and IL-1\u03b2 in microglia. Cytoplasmic accumulation of mutant SOD1 was sensed by an ASC containing inflammasome and antagonized by autophagy, limiting caspase-1\u2013mediated inflammation. Notably, mutant SOD1 induced IL-1\u03b2 correlated with amyloid-like misfolding and was independent of dismutase activity. Deficiency in caspase-1 or IL-1\u03b2 or treatment with recombinant IL-1 receptor antagonist (IL-1RA) extended the lifespan of G93A-\n SOD1<\/jats:italic>\n transgenic mice and attenuated inflammatory pathology. These findings identify microglial IL-1\u03b2 as a causative event of neuroinflammation and suggest IL-1 as a potential therapeutic target in ALS.\n <\/jats:p>","DOI":"10.1073\/pnas.1002396107","type":"journal-article","created":{"date-parts":[[2010,6,29]],"date-time":"2010-06-29T00:54:15Z","timestamp":1277772855000},"page":"13046-13050","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":290,"title":["Mutant superoxide dismutase 1-induced IL-1\u03b2 accelerates ALS pathogenesis"],"prefix":"10.1073","volume":"107","author":[{"given":"Felix","family":"Meissner","sequence":"first","affiliation":[{"name":"Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaaweh","family":"Molawi","sequence":"additional","affiliation":[{"name":"Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Zychlinsky","sequence":"additional","affiliation":[{"name":"Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21543"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200908164"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2536"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10191"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.240305897"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.335"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00730.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1603"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20919"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2161"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1830709"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03029"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1256"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-3-2"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80272-X"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1559"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700477104"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp260"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1836"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.05.020"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.9.1273"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.03.001"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-007-0748-y"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1002396107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:45:36Z","timestamp":1649789136000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1002396107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,20]]},"references-count":28,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2010,7,20]]}},"alternative-id":["10.1073\/pnas.1002396107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1002396107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,20]]},"assertion":[{"value":"2010-07-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}