{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:24:21Z","timestamp":1791822261690,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008714","name":"Motor Neurone Disease Research Institute of Australia","doi-asserted-by":"publisher","award":["C0021192"],"award-info":[{"award-number":["C0021192"]}],"id":[{"id":"10.13039\/100008714","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008714","name":"Motor Neurone Disease Research Institute of Australia","doi-asserted-by":"publisher","award":["K0020795"],"award-info":[{"award-number":["K0020795"]}],"id":[{"id":"10.13039\/100008714","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["D0018642"],"award-info":[{"award-number":["D0018642"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Degeneration of the distal neuromuscular circuitry is a hallmark pathology of Amyotrophic Lateral Sclerosis (<jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>). The potential for microtubule dysfunction to be a critical pathophysiological mechanism in the destruction of this circuitry is increasingly being appreciated. Stabilization of microtubules to improve neuronal integrity and pathology has been shown to be a particularly favourable approach in other neurodegenerative diseases. We present evidence here that treatment with the microtubule\u2010targeting compound Epothilone D (EpoD) both positively and negatively affects the spinal neuromuscular circuitry in the <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>1<jats:sup>G93A<\/jats:sup> mouse model of <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>1<jats:sup>G93A<\/jats:sup> mice were treated every 5 days with 2 mg\/kg EpoD. Evaluation of motor behaviour, neurological phenotype and survival was completed, with age\u2010dependent histological characterization also conducted, using the <jats:italic>thy1<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">YFP<\/jats:styled-content> mouse. Motor neuron degeneration, axonal integrity, neuromuscular junction (<jats:styled-content style=\"fixed-case\">NMJ<\/jats:styled-content>) health and gliosis were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EpoD treatment prevented loss of the spinal motor neuron soma, and distal axon degeneration, early in the disease course. This, however, was not associated with protection of the <jats:styled-content style=\"fixed-case\">NMJ<\/jats:styled-content> synapse and did not improve motor phenotype or clinical progression. EpoD administration was also found to be neurotoxic at later disease stages. This was evidenced by accelerated motor neuron cell body loss, increasing gliosis, and was associated with detrimental outcomes to motor behaviour, clinical assessment and survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results suggest that EpoD accelerates disease progression in the <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>1<jats:sup>G93A<\/jats:sup> mouse model of <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>, and highlights that the pathophysiological involvement of microtubules in <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> is an evolving and underappreciated phenomenon.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12473","type":"journal-article","created":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T05:08:42Z","timestamp":1517288922000},"page":"590-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Epothilone D accelerates disease progression in the SOD1<sup>G93A<\/sup> mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-1489","authenticated-orcid":false,"given":"J. A.","family":"Clark","sequence":"first","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Blizzard","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Breslin","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Yeaman","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health Parkville Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Chuckowree","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. C.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania Hobart Tas. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt085"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140316"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.10.009"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/364362c0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02534.2000"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2003.10.004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2005000600015"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.09.027"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3626"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703434200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5827"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006869107"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.08.010"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00204"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2016.04.007"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.12.046"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4922-11.2012"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3059-10.2010"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep01837"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13585"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-59"},{"key":"e_1_2_7_24_1","first-page":"2325","article-title":"Epothilones, a new class of microtubule\u2010stabilizing agents with a taxol\u2010like mechanism of action","volume":"55","author":"Bollag DM","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S77342"},{"key":"e_1_2_7_26_1","first-page":"1","article-title":"Working with ALS mice: guidelines for preclinical testing & colony management","author":"Leitner M","year":"2009","journal-title":"The Jackson Lab"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960701856300"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960701292837"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200305230-00029"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp055"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.06.019"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.11.048"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.05.045"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906809106"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.018606"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20704"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2011.02.022"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)01954-5"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2016.03.003"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00343"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2958"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201148"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406361102"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.049"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt028"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64575"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg254"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00060"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00252"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:NEUR.0000020628.36013.88"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.66.032102.113328"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00944-8"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/718987"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.0543"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-015-9580-6"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0049-0"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385883-2.00002-3"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.4161\/sgtp.28430"},{"key":"e_1_2_7_60_1","first-page":"279","article-title":"Rac1 at the crossroad of actin dynamics and neuroinflammation in Amyotrophic Lateral Sclerosis","volume":"8","author":"D'Ambrosi N","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506216200"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.431957"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.138"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5056418"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12982-015-0038-3"},{"key":"e_1_2_7_66_1","volume-title":"Statistical models in epidemiology","author":"Clayton D","year":"2013"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/30.6.1332"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12473","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T08:44:49Z","timestamp":1695026689000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,27]]},"references-count":66,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/nan.12473"],"URL":"https:\/\/doi.org\/10.1111\/nan.12473","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,27]]},"assertion":[{"value":"2017-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}