{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:00:57Z","timestamp":1773154857838,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173552"],"award-info":[{"award-number":["82173552"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The relationship between environmental neurotoxicant exposure and neurodegenerative diseases is being extensively investigated. Carbon disulfide, a classic neurotoxicant and prototype of dithiocarbamates fungicides and anti-inflammatory agents, has been detected in urban adults, raising questions about whether exposure to carbon disulfide is associated with a high incidence of neurodegenerative diseases. Here, using rat models and SH-SY5Y cells, we investigated the possible mechanistic linkages between carbon disulfide neurotoxicity and the expression of TDP-43 protein, a marker of amyotrophic lateral sclerosis\/frontotemporal lobar degeneration. Our results showed that rats exhibited severe dyskinesia and increased TDP-43 expression in the spinal cord following carbon disulfide exposure. Moreover, carbon disulfide exposure induced abnormal cytoplasmic localization and phosphorylation of TDP-43 in motor neurons. Importantly, carbon disulfide treatment led to the accumulation of TDP-43 in the mitochondria of motor neurons and resulted in subsequent mitochondrial damage, including mitochondrial structural disruption, mitochondrial respiratory chain complex I inhibition, and impaired VCP\/p97-dependent mitophagy. In summary, our study provides support for carbon disulfide exposure-mediated TDP-43 mislocalization and mitochondrial dysfunction, contributes to understanding the pathogenesis of environmental neurotoxin-induced neurodegeneration, and provides inspiration for potential therapeutic strategies.<\/jats:p>","DOI":"10.1093\/cercor\/bhad526","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T07:11:57Z","timestamp":1704697917000},"source":"Crossref","is-referenced-by-count":6,"title":["Carbon disulfide induces accumulation of TDP-43 in the cytoplasm and mitochondrial dysfunction in rat spinal cords"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3903-1270","authenticated-orcid":false,"given":"Zhidan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Toxicology and Nutrition , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalong","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Nutrition , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shulin","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Nutrition , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Nutrition , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Nutrition , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan 250012, Shandong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"2024020511084100700_ref1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13024-016-0102-7","article-title":"Targeting TDP-43 phosphorylation by casein kinase-1\u03b4 inhibitors: a novel strategy for the treatment of frontotemporal dementia","volume":"11","author":"Alquezar","year":"2016","journal-title":"Mol Neurodegener"},{"key":"2024020511084100700_ref2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"2024020511084100700_ref3","doi-asserted-by":"crossref","first-page":"E736","DOI":"10.1073\/pnas.1222809110","article-title":"ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43","volume":"110","author":"Arnold","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024020511084100700_ref4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-021-04199-3","article-title":"Structure of pathological TDP-43 filaments from ALS with FTLD","volume":"601","author":"Arseni","year":"2022","journal-title":"Nature"},{"issue":"1","key":"2024020511084100700_ref5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13024-017-0177-9","article-title":"Dioxins and related environmental contaminants increase TDP-43 levels","volume":"12","author":"Ash","year":"2017","journal-title":"Mol Neurodegener"},{"issue":"1","key":"2024020511084100700_ref6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/toxsci\/kfy267","article-title":"Heavy metal neurotoxicants induce ALS-linked TDP-43 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fragments in ALS and FTLD","volume":"13","author":"Berning","year":"2019","journal-title":"Front Neurosci"},{"key":"2024020511084100700_ref10","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1073\/pnas.1202922109","article-title":"Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability","volume":"109","author":"Bilican","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024020511084100700_ref11","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as multifaceted regulators of cell death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024020511084100700_ref12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1039\/C6CS00585C","article-title":"Carbon disulfide. Just toxic or also bioregulatory and\/or therapeutic?","volume":"46","author":"DeMartino","year":"2017","journal-title":"Chem Soc Rev"},{"key":"2024020511084100700_ref13","doi-asserted-by":"crossref","first-page":"e106177","DOI":"10.15252\/embj.2020106177","article-title":"HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations","volume":"40","author":"Fazal","year":"2021","journal-title":"EMBO J"},{"key":"2024020511084100700_ref14","doi-asserted-by":"crossref","first-page":"106022","DOI":"10.1016\/j.nbd.2023.106022","article-title":"SBT-272 improves TDP-43 pathology in ALS upper motor neurons by modulating mitochondrial integrity, motility, and function","volume":"178","author":"Gautam","year":"2023","journal-title":"Neurobiol Dis"},{"key":"2024020511084100700_ref15","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","article-title":"Disruption of mitochondrial complex I induces progressive 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