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Previously, we generated a <jats:italic>Caenorhabditis elegans<\/jats:italic> model of ALS, in which the expression of <jats:italic>dnc-1<\/jats:italic>, the homologous gene of human <jats:italic>dynactin-1<\/jats:italic>, is knocked down (KD) specifically in motor neurons. This <jats:italic>dnc-1<\/jats:italic> KD model showed progressive motor defects together with axonal and neuronal degeneration, as observed in ALS patients. In the present study, we established a behavior-based, automated, and quantitative drug screening system using this <jats:italic>dnc-1<\/jats:italic> KD model together with Multi-Worm Tracker (MWT), and tested whether 38 candidate neuroprotective compounds could improve the mobility of the <jats:italic>dnc-1<\/jats:italic> KD animals. We found that 12 compounds, including riluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the <jats:italic>dnc-1<\/jats:italic> KD animals. Nifedipine, a calcium channel blocker, most robustly ameliorated the motor deficits as well as axonal degeneration of <jats:italic>dnc-1<\/jats:italic> KD animals. Nifedipine also ameliorated the motor defects of other motor neuronal degeneration models of <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic>, including <jats:italic>dnc-1<\/jats:italic> mutants and human TAR DNA-binding protein of 43\u2009kDa overexpressing worms. Our results indicate that <jats:italic>dnc-1<\/jats:italic> KD in <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic> is a useful model for the screening of drugs against motor neuron degeneration, and that MWT is a powerful tool for the behavior-based screening of drugs.<\/jats:p>","DOI":"10.1038\/s41598-019-46642-6","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T10:03:41Z","timestamp":1562925821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["A behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Kensuke","family":"Ikenaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-2170","authenticated-orcid":false,"given":"Yuki","family":"Tsukada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadamasa","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Nakadera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0874-7542","authenticated-orcid":false,"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-9311","authenticated-orcid":false,"given":"Masahisa","family":"Katsuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4769-5922","authenticated-orcid":false,"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikue","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"46642_CR1","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1002\/ana.20379","volume":"57","author":"YM Jiang","year":"2005","unstructured":"Jiang, Y. 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