The contribution of C. elegans neurogenetics to understanding neurodegenerative diseases

Abstract

Since Caenorhabditis elegans was first introduced as a genetic model organism by Sydney Brenner, researchers studying it have made significant contributions in numerous fields including investigations of the pathophysiology of neurodegenerative diseases. The simple anatomy, optical transparency, and short life-span of this small nematode together with the development and curation of many openly shared resources (including the entire genome, cell lineage and the neural map of the animal) allow researchers using C. elegans to move their research forward rapidly in an immensely collaborative community. These resources have allowed researchers to use C. elegans to study the cellular processes that may underlie human diseases. Indeed, many disease-associated genes have orthologs in C. elegans, allowing the effects of mutations in these genes to be studied in relevant and reproducible neuronal cell-types at single-cell resolution in vivo. Here we review studies that have attempted to establish genetic models of specific human neurodegenerative diseases (ALS, Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease) in C. elegans and what they have contributed to understanding the molecular and genetic underpinnings of each disease. With continuous advances in genome engineering, research conducted using this small organism first established by Brenner, Sulston and their contemporaries will continue to contribute to the understanding of human nervous diseases.

Keywords:

• C. elegans
• nervous diseases
• neurodegeneration
• neurodegenerative diseases

Acknowledgements

The authors would like to thank Troy A. McDiarmid and Alex J. Yu for helpful comments to the manuscript. They would also like to thank Lexi D. Kepler for help making the figures.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a Natural Sciences and Engineering Research Council of Canada under the Canada Graduate Scholarships – Canadian Graduate Scholarship Masters to J.L. as well as by the Natural Sciences and Engineering Research Council of Canada under project grant [NSERC RGPIN-2019–05558] and Canadian Institutes of Health Research under project grant [CIHR PJT 165947] to C.H.R.