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We performed lipidomics on C9 ALS\/FTD\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS\/FTD flies PUFAs yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of C9 ALS\/FTD flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor-induced neuronal death in iPS cell neurons of patients with both C9 and TDP-43 ALS\/FTD. These data implicate neuronal fatty acid saturation in the pathogenesis of ALS\/FTD and suggest that interventions to increase neuronal PUFA levels may be beneficial.\n                  <\/jats:p>","DOI":"10.1038\/s41593-025-01889-3","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T05:01:59Z","timestamp":1740459719000},"page":"737-747","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Neuronal polyunsaturated fatty acids are protective in ALS\/FTD"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-7908","authenticated-orcid":false,"given":"Ashling","family":"Giblin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Cammack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek","family":"Blomberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharifah","family":"Anoar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-9719","authenticated-orcid":false,"given":"Alla","family":"Mikheenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-9016","authenticated-orcid":false,"given":"Mireia","family":"Carcol\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-2023","authenticated-orcid":false,"given":"Magda L.","family":"Atilano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-4926","authenticated-orcid":false,"given":"Alex","family":"Hull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunxin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Coneys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-3332","authenticated-orcid":false,"given":"Yassene","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6363-0857","authenticated-orcid":false,"given":"Damien","family":"Olivier-Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian Y.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri J.","family":"Kinghorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-0411","authenticated-orcid":false,"given":"Teresa","family":"Niccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-5325","authenticated-orcid":false,"given":"Alyssa N.","family":"Coyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"van der Kant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7389-0348","authenticated-orcid":false,"given":"Tammaryn","family":"Lashley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-1894","authenticated-orcid":false,"given":"Martin","family":"Giera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-0094","authenticated-orcid":false,"given":"Linda","family":"Partridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-5534","authenticated-orcid":false,"given":"Adrian M.","family":"Isaacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"1889_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","volume":"72","author":"M DeJesus-Hernandez","year":"2011","unstructured":"DeJesus-Hernandez, M. et al. 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