{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:39:13Z","timestamp":1786743553226,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["MND202003011470"],"award-info":[{"award-number":["MND202003011470"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"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>TDP\u201043 mislocalization and aggregation are common features of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms underlying the transition of nuclear TDP\u201043 to cytoplasmic aggregates, and their contribution to disease pathogenesis, remain poorly understood. To address this gap, we present a methodology to chemically control the assembly and disassembly of cytoplasmic TDP\u201043 condensates. By fusing TDP\u201043 to a phase separation\u2013prone protein scaffold, we can induce the formation of cytoplasmic TDP\u201043 condensates or, conversely, promote nuclear localization upon addition of a disassembly molecule. TDP\u201043 accumulates into various assemblies, ranging from submicrometric puncta to larger aggregate\u2010like structures that display hallmarks of proteinopathy in a concentration\u2010dependent manner. Furthermore, oxidative stress drives the maturation of TDP\u201043 assemblies from puncta into aggregates through interactions with stress granule components. Finally, we show that cytoplasmic TDP\u201043 aggregates deplete nuclear endogenous TDP\u201043 and induce cytotoxicity. Collectively, these findings highlight the local cytoplasmic concentration of TDP\u201043 and stress exposure as key determinants in the onset of TDP\u201043 proteinopathy, providing a relevant model to study pathological TDP\u201043 aggregation.<\/jats:p>","DOI":"10.1111\/febs.70429","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:11:06Z","timestamp":1769775066000},"page":"4167-4184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Concentration\u2010dependent cytoplasmic phase separation of\n                    <scp>TDP<\/scp>\n                    \u201043 drives aggregation and proteinopathy"],"prefix":"10.1111","volume":"293","author":[{"given":"Pauline","family":"Combe","sequence":"first","affiliation":[{"name":"CPCV, Department of Chemistry, \u00c9cole Normale Sup\u00e9rieure PSL University, Sorbonne Universit\u00e9, CNRS  Paris 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