{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:05:04Z","timestamp":1784167504447,"version":"3.55.0"},"reference-count":8,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    TDP\u201043 is a nuclear RNA\u2010binding protein implicated in neurodegenerative diseases such as ALS and FTLD, where it becomes mislocalized to the cytoplasm and forms pathological aggregates. These aggregates are thought to arise through liquid\u2013liquid phase separation, a process by which proteins form dynamic, membrane\u2010less condensates that can mature into solid structures. To better understand this process, the authors developed ArtiTDP43, a chemically controllable system that enables reversible formation of TDP\u201043 condensates in cells. Using this tool, they showed that TDP\u201043 forms different structures depending on its concentration: small liquid\u2010like puncta, intermediate condensates associated with stress granules, and large solid aggregates resembling disease pathology. These transitions are reversible at early stages but become irreversible as aggregates solidify. The study by Combe\n                    <jats:italic>et\u00a0al.<\/jats:italic>\n                    demonstrates that increasing cytoplasmic TDP\u201043 concentration drives a liquid\u2010to\u2010solid transition, while oxidative stress accelerates this process and promotes pathological features such as phosphorylation and p62 recruitment. Importantly, formation of cytoplasmic aggregates leads to depletion of nuclear TDP\u201043 and increased cell death, indicating toxicity. Overall, the findings establish a mechanistic link between phase separation, aggregation, and cytotoxicity in TDP\u201043 proteinopathies. ArtiTDP43 provides a powerful tool to study early disease mechanisms and explore therapeutic strategies aimed at preventing pathological aggregation or maintaining normal TDP\u201043 dynamics.\n                  <\/jats:p>","DOI":"10.1111\/febs.70577","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T11:36:38Z","timestamp":1777721798000},"page":"4145-4148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the role of phase separation in\n                    <scp>TDP<\/scp>\n                    \u201043 pathogenesis with\n                    <scp>ArtiTDP43<\/scp>"],"prefix":"10.1111","volume":"293","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5855-4522","authenticated-orcid":false,"given":"Eric","family":"Chevet","sequence":"first","affiliation":[{"name":"Inserm U1242 University of Rennes  Rennes France"},{"name":"Centre de Lutte contre le Cancer Eug\u00e8ne Marquis  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.06.004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3121"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2021.07.004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.6b01088"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70429"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.04.025"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00513-7"},{"key":"e_1_2_5_9_1","article-title":"TDP\u201043 pathology is linked\u00a0to\u00a0motor neuron loss but is independent of\u00a0stress\u00a0granules in vivo","volume":"13","author":"Dubinski A","year":"2026","journal-title":"bioRxiv"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.70577","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.70577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:37:19Z","timestamp":1784165839000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.70577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":8,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/febs.70577"],"URL":"https:\/\/doi.org\/10.1111\/febs.70577","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]},"assertion":[{"value":"2026-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}