{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:48:35Z","timestamp":1790916515659,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012007","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG079898"],"award-info":[{"award-number":["R01AG079898"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG078788"],"award-info":[{"award-number":["R01AG078788"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG076493"],"award-info":[{"award-number":["R01AG076493"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALS Ride For Life","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Waterwheel Foundation"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    A key pathological feature of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) is the loss of nuclear localization and accumulation of cytoplasmic inclusions of TAR-DNA binding protein 43 (TDP-43). TDP-43 is a nucleic acid-binding protein involved in transcriptional repression, mRNA splicing, and the regulation of retrotransposable elements (RTEs) and endogenous retroviruses (ERVs). RTEs\/ERVs are mobile virus-like genetic elements that constitute about 45% of our genome and encode the capacity to replicate through an RNA intermediate and insert cDNA copies at\n                    <jats:italic>de novo<\/jats:italic>\n                    chromosomal locations. A causal role of RTEs\/ERVs has been demonstrated in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    in mediating both intracellular toxicity of TDP-43 and the intercellular spread of toxicity from glia to neurons. RTEs\/ERVs are inappropriately expressed in postmortem tissues from ALS, FTD, and Alzheimer\u2019s Disease (AD) patients, but the role of RTEs\/ERVs has not yet been examined in a vertebrate model of TDP-43 pathology. We utilized established transgenic mouse models that overexpress moderate levels of human wild-type TDP-43 or a mutant version with a specific ALS-causal Q331K amino acid substitution, together with a LINE-1-EGFP retrotransposon indicator line. We found that TDP-43 animals exhibit broad expression of RTEs\/ERVs with LINE-1 retrotransposition in glia and neurons in the motor cortex. Expression begins with onset of neurological phenotypes, earlier in hTDP-43-Q331K animals and later in hTDP-43-WT. The LINE-1-EGFP retrotransposition reporter transiently labels spatially clustered groups of neurons and glia at the time of onset of motor symptoms, while EGFP-labeled neurons undergo cell death and are therefore lost over time. Unlabeled cells also die as a function of distance from the clusters of LINE-1-EGFP labeled neurons and glial cells. Together, these findings support the hypothesis that TDP-43 pathology triggers RTE\/ERV expression in the motor cortex, that such expression marks cells for programmed cell death, with cell non-autonomous effects on nearby neurons and glial cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012007","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T18:57:45Z","timestamp":1767034665000},"page":"e1012007","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["LINE-1 retrotransposition in a mouse TDP-43 model of neurodegeneration marks motor cortex neurons for cell-intrinsic and cell non-autonomous programmed cell death"],"prefix":"10.1371","volume":"21","author":[{"given":"Shreevidya","family":"Korada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-3655","authenticated-orcid":true,"given":"Oliver H.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter C.","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-8392","authenticated-orcid":true,"given":"Molly Gale","family":"Hammell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-7444","authenticated-orcid":true,"given":"Josh","family":"Dubnau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-537X","authenticated-orcid":true,"given":"Roger B.","family":"Sher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"pgen.1012007.ref001","doi-asserted-by":"crossref","first-page":"117999","DOI":"10.1016\/j.jns.2021.117999","article-title":"The ALS-FTD spectrum","volume":"429","author":"P Lillo","year":"2021","journal-title":"J Neurol Sci"},{"issue":"3","key":"pgen.1012007.ref002","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging 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Lorenzl","year":"2003","journal-title":"Neurochem Int"},{"issue":"4","key":"pgen.1012007.ref047","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0092-8674(00)80244-5","article-title":"Skeletal and CNS defects in Presenilin-1-deficient mice","volume":"89","author":"J Shen","year":"1997","journal-title":"Cell"},{"issue":"29","key":"pgen.1012007.ref048","doi-asserted-by":"crossref","first-page":"16991","DOI":"10.1074\/jbc.271.29.16991","article-title":"Selective loss of cerebral keratan sulfate in Alzheimer\u2019s disease","volume":"271","author":"B Lindahl","year":"1996","journal-title":"J Biol Chem"},{"issue":"4","key":"pgen.1012007.ref049","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0896-6273(91)90052-2","article-title":"The molecular pathology of Alzheimer\u2019s disease","volume":"6","author":"DJ 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