Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans

Abstract

The elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode Caenorhabditis elegans (C. elegans) emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative C. elegans models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect. We exemplify applications of high-throughput genetic and drug screenings to illustrate the potential of C. elegans to probe novel therapeutic targets. This review highlights the utility of C. elegans as a comprehensive and versatile platform for the dissection of neurodegenerative diseases at the molecular level.

Keywords: C. elegans; C9ORF72; FUS; SOD1; TDP-43; amyloid β1-42; gain-of-toxicity; polyQ; tau; α-synuclein.

Figure 1

A simplified anatomical sketch of C. elegans denoting tissues of transgene expression applied in the reviewed disease models. Regions of expression are separated into two organ systems with 4 sub-divisions of specific neurodegenerative diseases. Green: nervous system; grey: muscular system.