Molecule demonstrates success controlling Parkinson’s-associated protein behaviour

The protein, which occurs notably in brain cells, regulates dopamine release and enables communication between neurones.

However, in cases of Parkinson’s, it forms clumps that causes cell death and a variety of symptoms associated with the disease including tremors and Parkinson’s-related dementias.

A team from the University of Bath, working with colleagues from Oxford and Bristol, developed a peptide fragment molecule capable of locking the protein into its desired active state.

When active for the purposes of binding and transporting dopamine, alpha-synuclein shapes itself from a flexible strand into a helix.

Working on a worm model of Parkinson’s, the researchers demonstrated that the fragment could prevent the protein from converting into toxic clumps.

Writing in JACS Au, they said the peptide treatment had helped to restore movement in the model.

The work was funded by Alzheimer’s Research UK, whose head of research Dr Julia Dudley said proof that the new molecule could prevent the misfolded protein buildup was “exciting” even though it was focused on an animal model.

“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 like Parkinson’s and dementia with Lewy bodies,” she said.

She added that the charity looked forward to the next stage, which could involve examining how the approach would work for humans. 

Professor Jody Mason from Bath’s department of life sciences commented: “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.”

Pic: Brano