Tiny Worms, Big Discoveries: C. Elegans as a Powerful Model for Parkinson’s Disease

In the field of neurodegenerative diseases, Parkinson’s disease poses a significant challenge to both affected patients and scientists. In addition to the motor-related symptoms of the disease, such as tremors, stiffness and balance problems, people with Parkinson’s can experience depression, anxiety, and hallucinations. While scientists and doctors know that Parkinson’s disease is a neurological disorder that affects dopamine-producing neurons, its cause continues to remain unknown and its cure is currently out of reach. Therefore, it may come as a big surprise to many that an unassuming worm is a key player in the attempt to demystify Parkinson’s disease.

Dr. Samantha Hughes, an assistant professor at Vrije Universiteit Amsterdam, describes what the worm, Caenorhabditis elegans or C. elegans, brings to the table. Hughes primarily focuses on C. elegans as a model to discover how humans in general can live longer, healthier lives. As Hughes explains, C. elegans is a species of nematode worm; it has a simple anatomy with a small number of cells, and is a hermaphrodite able to self-fertilize. The worm is also transparent, allowing scientists to visualize cellular processes, including embryonic development, as they occur in vivo or in the lab.

“Each worm has about 300 genetic offspring, and we can synchronize them so that they are all the same age and they all develop at the same time.”

Dr. Samantha Hughes

So how can C. elegans help us understand Parkinson’s disease? Unlike mice, another common animal model of neurological diseases, C. elegans have a short life cycle, living only 3-4 weeks. C. elegans also have many offspring, and they can reproduce in only a few days. This allows for experiments to be done in a reasonably short amount of time. It can also cost less money and feature many specimens, increasing data collection accuracy. Dr. Hughes shared, “Each worm has about 300 genetic offspring, and we can synchronize them so that they are all the same age and they all develop at the same time.”

These unique characteristics, combined with the relative ease of introducing human Parkinson’s disease genes into worms, can help us observe how genetic alterations influence the worm’s behavior, movement and lifespan. 

Common models for Parkinson’s include worms that express alpha-synuclein, a neural protein that aggregates in the disease, as well as worms with specific gene deletions. As Hughes explains, these worms display symptoms of Parkinson’s disease, such as the loss of dopamine neurons, increased sensitivity to stress, and movement issues, helping scientists better understand how Parkinson’s develops and what factors contribute to the disease. “I take the human gene alpha synuclein and I attach that to a Green Fluorescent Protein tag that allows me to see it and inject it in the worm… I watch how this [protein] aggregates change over time. Does it get bigger? Clump together? Move around? And then I treat the worms with different drugs and compounds to see if I can get rid of all these plaques and make a treatment,” said Dr. Hughes.

While the connection between these worms and neurodegenerative diseases is still being identified, there is great potential for learning more about Parkinson’s, possible treatments, and future impacts on neurological diseases as a whole. 

In the future, C. elegans could have a significant effect on Parkinson’s disease research; “The benefit of the worms in the field is that we can use them to understand the mechanisms of Parkinson’s,” said Hughes. She asks questions like, “How does the disease come about? What are the genes that cause it? What are the environmental compounds that cause Parkinson’s?” 

There is hope that the research may uncover new drug targets, lead to new medical approaches for early detection, help calculate risk assessments, and more. In addition, findings gathered through C. elegans and Parkinson’s disease research may encourage continued exploration to advance human understanding and treatment of the disease. 

But, it is important to remember that C. elegans are not the perfect model organisms for Parkinson’s disease; “All fields, [including Parkinson’s disease] need to test things in many different systems to get a proper answer,” said Dr. Hughes. Researching different model organisms, such as fruit flies and mice, can help scientists collectively find answers that benefit humans. But for now, some researchers are looking towards these tiny, transparent worms to show the way.