The team has successfully demonstrated it works in an animal model of Parkinson’s and hopes that, in the future, this could lead to a treatment that slows the progression of the disease.
Alpha-synuclein is a protein naturally found mainly in brain cells (neurons) where it regulates the release of neurotransmitters such as dopamine, allowing communication between the neurons.
In Parkinson’s disease, this protein sticks together into toxic clumps that cause nerve cell death and leads to patients suffering from symptoms such as tremors, difficulties moving and muscle stiffness. Although there are treatments available to relieve symptoms, there is currently no cure.
Normally, alpha-synuclein’s natural or “native state” is like a flexible strand, but when active it shapes itself into a helix, which is critical for its function in binding and transporting parcels of dopamine.
The team engineered a peptide fragment that locks alpha-synuclein into its healthy shape, blocking its conversion into the toxic clumps that cause nerve cell death.
Laboratory tests showed the peptide is stable, penetrates brain-like cells and restores movement while reducing protein deposits in a worm model of Parkinson’s.
This breakthrough, published in the journal JACS Au, demonstrates the potential of rational peptide design to transform large, unstable proteins into compact drug-like molecules.
The findings mark a significant step towards developing new peptide-based treatments for currently untreatable neurodegenerative conditions.
Professor Jody Mason, from the Department of Life Sciences at the University of Bath, said: “Our work shows that it is possible to rationally design small peptides that not only prevent harmful protein aggregation but also function inside living systems."
“This opens an exciting path towards new therapies for Parkinson’s and related diseases, where treatment options remain extremely limited.”
Dr Julia Dudley, Head of Research at Alzheimer’s Research UK, which funded the research, said: “Dementia isn’t an inevitable part of ageing; it’s caused by diseases such as Alzheimer’s. To make progress towards a cure for all forms of dementia, we need research focused on developing a broad range of treatments that can slow, stop and ultimately reverse these diseases.
“Although this is early research in an animal model, it's exciting to see that this new molecule can prevent the build-up of misfolded alpha-synuclein."
“By stabilising alpha-synuclein in its healthy form, this could open the door to a new class of treatments that could slow progression in diseases such as Parkinson’s and dementia with Lewy bodies. We look forward to seeing this research taken to the next stage, potentially exploring how it would work in people."
“We’re delighted to see such promising advances from Alzheimer’s Research UK funded work opening up new avenues for treatments of the future, and the potential to change the lives of those affected by neurodegenerative diseases.”
Further research is needed, but the team hopes that continued progress will enable these and similar molecules to advance towards clinical testing in the coming years.