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Studying mutations in the gene which encodes TDP-43,\n                    <jats:italic>TARDBP<\/jats:italic>\n                    , provides a valuable opportunity to gain insight into how TDP-43 dysfunction alters cellular homoeostasis. Our group has previously developed a TDP-43\n                    <jats:sup>M337V<\/jats:sup>\n                    mouse embryonic stem cell-derived motor neuron (mESC-MN) model, which expresses a single copy of the human\n                    <jats:italic>TARDBP<\/jats:italic>\n                    gene expressing the pathogenic M337V mutation at low levels. Here, we perform extensive phenotypic characterisation of this model, and show that TDP-43\n                    <jats:sup>M337V<\/jats:sup>\n                    leads to reduced MN viability, impaired axonal transport and reduced basal glycolysis compared to TDP-43\n                    <jats:sup>WT<\/jats:sup>\n                    controls. Altered neuronal viability and function occurs in the absence of TDP-43 mislocalisation or aggregation, suggesting \u2018proteinopathy\u2019 is downstream of these ALS-relevant phenotypes. These findings provide further support for a link between TDP-43 dyshomeostasis, cellular bioenergetics and axonal transport and suggest these pathways warrant further investigation as targets for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08437-2","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T22:03:32Z","timestamp":1769897012000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mutant TDP-43 drives impairments in axonal transport and glycolysis in a mouse stem-cell-derived motor neuron model of amyotrophic lateral sclerosis (ALS)"],"prefix":"10.1038","volume":"17","author":[{"given":"Emily","family":"Carroll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Scaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris-Stefania","family":"Pasniceanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra","family":"Dafinca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Candalija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5490-1697","authenticated-orcid":false,"given":"Kevin","family":"Talbot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"8437_CR1","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1111\/ene.14393","volume":"27","author":"P Masrori","year":"2020","unstructured":"Masrori P, Van Damme P. 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