By University of Bath
October 5, 2025

Researchers have designed a peptide that stabilizes a key brain protein linked to Parkinson’s.

Scientists from the University of Bath, working with colleagues at the Universities of Oxford and Bristol, have created a new molecule that stops a key protein from clumping together in the brain. This protein, called alpha-synuclein, is linked to Parkinson’s disease and certain forms of dementia.

Alpha-synuclein is a protein found mainly in brain cells (neurons), where it helps control the release of chemical messengers such as dopamine, which allow neurons to communicate with each other.

In people with Parkinson’s disease, alpha-synuclein begins to stick together, forming harmful clusters that damage and kill nerve cells. This process triggers the movement-related symptoms of the disease, including tremors, stiffness, and difficulty controlling motion. Although current medications can ease these symptoms, there is still no cure for Parkinson’s.
Stabilizing the Protein’s Natural State

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.”

Expert Reactions and Future Potential

Dr Julia Dudley, Head of Research at Alzheimer’s Research UK, which funded the research, said:

“Dementia isn’t an inevitable part of aging; it’s caused by diseases like 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.

“By stabilizing alpha-synuclein in its healthy form, this could open the door to a new class of treatments that could slow progression in diseases like Parkinson’s and dementia with Lewy bodies.