A behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron disease

Kensuke Ikenaka, Yuki Tsukada, Andrew C. Giles, Tadamasa Arai, Yasuhito Nakadera, Shunji Nakano, Kaori Kawai, Hideki Mochizuki, Masahisa Katsuno, Gen Sobue, Ikue Mori

Research output: Contribution to journalArticlepeer-review


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, for which there is no effective treatment. Previously, we generated a Caenorhabditis elegans model of ALS, in which the expression of dnc-1, the homologous gene of human dynactin-1, is knocked down (KD) specifically in motor neurons. This dnc-1 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 dnc-1 KD model together with Multi-Worm Tracker (MWT), and tested whether 38 candidate neuroprotective compounds could improve the mobility of the dnc-1 KD animals. We found that 12 compounds, including riluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the dnc-1 KD animals. Nifedipine, a calcium channel blocker, most robustly ameliorated the motor deficits as well as axonal degeneration of dnc-1 KD animals. Nifedipine also ameliorated the motor defects of other motor neuronal degeneration models of C. elegans, including dnc-1 mutants and human TAR DNA-binding protein of 43 kDa overexpressing worms. Our results indicate that dnc-1 KD in C. elegans 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.

Original languageEnglish
Article number10104
JournalScientific reports
Issue number1
Publication statusPublished - 2019 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'A behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron disease'. Together they form a unique fingerprint.

Cite this