Innovative Peptide 'Switch' Developed to Maintain Healthy Form of Parkinson's-Linked Protein

Researchers from the University of Bath, collaborating with experts from Oxford and Bristol, have created a novel molecule aimed at combating Parkinson's disease by preventing the harmful aggregation of alpha-synuclein, a protein implicated in the condition. The team’s breakthrough demonstrates that this engineered peptide effectively keeps alpha-synuclein in its natural, functional shape, inhibiting its conversion into toxic clumps that lead to nerve cell degeneration.

Alpha-synuclein is primarily found in brain neurons, where it plays a crucial role in neurotransmitter release, including dopamine, facilitating communication between nerve cells. However, in Parkinson's disease, alpha-synuclein misfolds and forms sticky aggregates, resulting in cell death, and subsequent symptoms such as tremors, rigidity, and difficulty moving. Current treatments largely address symptoms rather than stopping disease progression.

The scientists designed a small peptide fragment that stabilizes alpha-synuclein's native structure, notably its helix form, which is essential for its normal function. Laboratory experiments revealed that this peptide remains stable, can penetrate brain-like cells, and in a worm Parkinson's model, it improved movement and reduced protein deposits.

Published in the journal JACS Au, this research highlights the potential of rational peptide design — creating compact, stable molecules capable of modulating complex proteins — to develop new therapies for neurodegenerative diseases. This approach could significantly advance treatment options for conditions like Parkinson’s and dementia with Lewy bodies.

Professor Jody Mason emphasized that this work shows the feasibility of designing small peptides that not only prevent harmful protein aggregation but also function inside living systems, opening new possibilities for drug development. Dr. Julia Dudley from Alzheimer's Research UK highlighted that stabilizing alpha-synuclein in its healthy form could pave the way for treatments that slow or halt disease progression, although further studies are necessary to translate these findings into human therapies.

Future efforts will focus on progressing this promising molecule through scientific and clinical testing, hopeful to lead to effective disease-modifying treatments for neurodegenerative disorders.