Using a Caenorhabditis elegans Parkinson’s Disease Model to Assess Disease Progression and Therapy Efficiency

Samantha Hughes*, Maritza van Dop, Nikki Kolsters, David van de Klashorst, Anastasia Pogosova, Anouk M. Rijs

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Despite Parkinson’s Disease (PD) being the second most common neurodegenerative disease, treatment options are limited. Consequently, there is an urgent need to identify and screen new therapeutic compounds that slow or reverse the pathology of PD. Unfortunately, few new therapeutics are being produced, partly due to the low throughput and/or poor predictability of the currently used model organisms and in vivo screening methods. Our objective was to develop a simple and affordable platform for drug screening utilizing the nematode Caenorhabditis elegans. The effect of Levodopa, the “Gold standard” of PD treatment, was explored in nematodes expressing the disease-causing α-synuclein protein. We focused on two key hallmarks of PD: plaque formation and mobility. Exposure to Levodopa ameliorated the mobility defect in C. elegans, similar to people living with PD who take the drug. Further, long-term Levodopa exposure was not detrimental to lifespan. This C. elegans-based method was used to screen a selection of small-molecule drugs for an impact on α-synuclein aggregation and mobility, identifying several promising compounds worthy of further investigation, most notably Ambroxol. The simple methodology means it can be adopted in many labs to pre-screen candidate compounds for a positive impact on disease progression.

Original languageEnglish
Article number512
Pages (from-to)1-19
Number of pages19
Issue number5
Early online date22 Apr 2022
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
Acknowledgments: We are grateful to the support provided by the HAN BioCentre, HAN University of Applied Sciences, and would especially like to thank Gijs Maassen and Ambra Miagostovich (HAN BioCentre) for their support on this project. Worm strains were provided by the Caenorhabditis Genetics Centre (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40OD010440).

Funding Information:
Funding: The authors gratefully acknowledge funding from the research program VICI with project number VI.C.192.024 and Aspasia (015.015.009) from the Dutch Research Council (NWO) awarded to A.M.R.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Ambroxol
  • C. elegans
  • Levodopa
  • lifespan
  • mobility
  • screening platform
  • therapeutics
  • α-synuclein aggregation


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