A molecule to fight Parkinson’s disease

Parkinson’s disease is the second most common neurodegenerative disorder worldwide, affecting more than 10 million people. Now, researchers at the University of Bath, in collaboration with the Universities of Oxford and Bristol, have developed a molecule that prevents the clumping and build-up of a protein linked to Parkinson’s disease and related dementias.

The team has successfully demonstrated that 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 lead to patients suffering from symptoms such as tremors, difficulties moving and muscle stiffness. Whilst treatments are available to relieve symptoms, there is currently no cure.

Normally, alpha-synuclein’s natural or “native state” is like a flexible strand. Still, when active, it forms a helix, which is critical for its function in binding and transporting 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 that the peptide is stable, penetrates brain-like cells, and restores movement while reducing protein deposits in a worm model of Parkinson’s disease.

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 this work shows that it is possible to rationally design small peptides that not only prevent harmful protein aggregation but also function inside living systems, and opens a door towards new therapies for Parkinson’s and related diseases that have limited treatment options.

Dr Julia Dudley, Head of Research at Alzheimer’s Research UK, which funded the research, said, “Dementia isn’t an inevitable part of ageing; diseases like Alzheimer’s cause it. 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, this new molecule can prevent the build-up of misfolded alpha-synuclein, she says.