{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:16:54Z","timestamp":1787588214941,"version":"build-2736575974"},"reference-count":74,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1124005"],"award-info":[{"award-number":["1124005"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1140386"],"award-info":[{"award-number":["1140386"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008714","name":"Motor Neurone Disease Research Institute of Australia","doi-asserted-by":"publisher","award":["1651"],"award-info":[{"award-number":["1651"]}],"id":[{"id":"10.13039\/100008714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS, and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43\u2009kDa (TDP\u201043), and understanding the effects of riluzole in models that closely recapitulate TDP\u201043 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in female transgenic mice that inducibly express nuclear localisation sequence (NLS)\u2010deficient human TDP\u201043 in neurons (\n                    <jats:italic>NEFH<\/jats:italic>\n                    \u2010tTA\/\n                    <jats:italic>tetO<\/jats:italic>\n                    \u2010hTDP\u201043\u0394NLS, \u2018rNLS8\u2019, mice). Riluzole treatment from the first day of hTDP\u201043\u0394NLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP\u201043 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8 mice, riluzole did not ameliorate this disease\u2010associated molecular phenotype. Likewise, riluzole did not alter the disease\u2010associated atrophy of hindlimb muscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late\u2010stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre\u2010type changes reminiscent of ALS in female rNLS8 mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways related to accumulation of TDP\u201043 pathology may be needed to develop better treatments for ALS.\n                  <\/jats:p>","DOI":"10.1111\/ejn.15422","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T20:34:29Z","timestamp":1628886869000},"page":"6237-6255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Riluzole does not ameliorate disease caused by cytoplasmic TDP\u201043 in a mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-6212","authenticated-orcid":false,"given":"Amanda L.","family":"Wright","sequence":"first","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences Macquarie University  Sydney New South Wales 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Health and Human Sciences Macquarie University  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-5512","authenticated-orcid":false,"given":"Rebecca","family":"San Gil","sequence":"additional","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences Macquarie University  Sydney New South Wales Australia"},{"name":"Neurodegeneration Pathobiology Laboratory, Queensland Brain Institute The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hedl","sequence":"additional","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences Macquarie University  Sydney New South Wales Australia"},{"name":"Neurodegeneration Pathobiology Laboratory, Queensland Brain 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