Summary: Researchers at the University of Toronto have developed an innovative screening system using tiny worms to rapidly identify compounds that could prevent harmful protein clumping associated with neurodegenerative diseases. Their initial screen of over 2,500 compounds identified 40 promising candidates that could inhibit amyloid formation, potentially opening new pathways for treating conditions like Alzheimer’s and Parkinson’s disease.
Journal: Nature Communications, September 30, 2024
Reading time: 4 minutes
A New Approach to Fighting Protein Aggregation
When proteins go rogue in our bodies, they can clump together to form dangerous structures called amyloids. These protein aggregates are implicated in over 50 human diseases, including some of our most devastating neurological conditions. Now, researchers have developed a innovative way to quickly identify compounds that might prevent this harmful protein clustering.
“Environmental factors, genetic mutations and other unknown factors can cause amyloid proteins or peptides to clump inside or outside the cell, forming structures that incrementally increase in complexity,” explains Muntasir Kamal, co-first author of the study and PhD graduate from the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research.
Breakthrough in Screening Speed
The research team’s new approach utilizes C. elegans, a tiny nematode worm, as a living test tube for screening potential therapeutic compounds. This innovative system allows researchers to evaluate thousands of compounds in a fraction of the time required by traditional methods.
“Most primary screens for amyloid binders have been conducted in cell-based or cell-free in vitro assays,” said Kamal. “When it comes to animal models, mice and rats are most commonly used to test experimental amyloid inhibitors. They both have their advantages, but neither compares to the free-living nematode C. elegans in terms of how quickly compounds can be screened with the worm model. It only takes one week to conduct an amyloid inhibitor screen with nematodes, which offer a more accurate representation of disease states than a petri dish.”
From Laboratory to Potential Treatments
The implications of this research extend far beyond the laboratory. The team has already identified 40 promising compounds from their initial screen of over 2,500 candidates, demonstrating the system’s effectiveness in finding potential therapeutic agents.
“We’ve developed a platform to rapidly screen compounds for amyloid growth suppressors,” said Peter Roy, principal investigator on the study and professor of molecular genetics at the Donnelly Centre and U of T’s Temerty Faculty of Medicine. “This platform can be used in preclinical studies to inform drug therapies. Ultimately, we hope to see results from testing amyloid binders in nematodes translate to treating neurodegenerative diseases in humans.”
Further Reading
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