{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:46:11Z","timestamp":1784619971617,"version":"3.55.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS078398"],"award-info":[{"award-number":["R01NS078398"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["F31NS092340"],"award-info":[{"award-number":["F31NS092340"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,9]]},"abstract":"<jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor neuron degeneration in vivo to gain a better understanding of ALS pathophysiology. We demonstrate that one miRNA, miR-146a, is downregulated in diseased motor neurons despite upregulation in bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mice with heterozygous animals demonstrating the largest benefit. A corresponding reduction in spinal cord gliosis but not motor neuron loss was observed. Finally, we observed that a proportion of miR-146a knockout animals develop spontaneous paralysis, motor neuron loss and chronic neuroinflammation with advanced age. Together these findings demonstrate that a single miRNA influences multiple aspects of motor neuron disease and highlights the complex role for neuroinflammation in ALS pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2526314123","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:33:41Z","timestamp":1780342421000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["miR-146a is a pleiotropic regulator of motor neuron degeneration"],"prefix":"10.1073","volume":"123","author":[{"given":"Dylan A.","family":"Galloway","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-4982","authenticated-orcid":false,"given":"Hunter L.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariah L.","family":"Hoye","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Shabsovich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6710-5147","authenticated-orcid":false,"given":"Kathleen M.","family":"Schoch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-5170","authenticated-orcid":false,"given":"Cindy V.","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-5511","authenticated-orcid":false,"given":"Timothy M.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20413"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1971"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.3155"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390203"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.07.017"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99081"},{"key":"e_1_3_4_9_2","first-page":"691","article-title":"Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue","volume":"140","author":"Kawamata T.","year":"1992","unstructured":"T. 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A. Galloway miR-146a is a pleiotropic regulator of motor neuron degeneration. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE329189. 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