Sticky protein hails new approach for treating Parkinson's

February 25, 2015

UK scientists have developed a peptide that sticks to the protein that causes Parkinson's disease, stopping it from killing brain cells. The research highlights a potential new route for slowing the progress of this incurable disease.

Parkinson's affects around 1 in 500 people in the UK. It's a progressive neurological condition where brain cells die causing a lack of the chemical dopamine, which acts as a messenger that coordinates movement. Parkinson's causes symptoms of tremor, rigidity and slowness of movement.

In Parkinson's, a protein called α-synuclein becomes misshapen and stacks together to form long toxic fibrils that kill the brain cells. A team of scientists led by the University of Bath, with funding from Parkinson's UK, has designed a peptide that binds to the faulty α-synuclein and stops fibrils from forming. Their research is published in the Journal of Biological Chemistry.

The researchers showed that the peptide halts the formation of fibrils in cells in vitro and stops them dying. The team anticipates that if developed into a treatment, the peptide could help slow the progression of this degenerative disease.

Dr Jody Mason, from the University of Bath's Department of Biology & Biochemistry, explained: "In Parkinson's, the protein called α-synuclein changes shape and stacks with other misshapen proteins.

"We've discovered a peptide that binds to the sticky part of the α-synuclein and covers it up, which stops the fibril growing.

"If you think of the misshapen α-synuclein proteins as Lego bricks which stack to form a tower; our peptide acts like a smooth brick that sticks to the α-synuclein and stops the tower from growing any bigger.

"This research is in the early stages, but the results so far are very encouraging. We still need to overcome many obstacles before this can be developed into a drug treatment, but these findings could herald a new approach to treating Parkinson's."

Co-author Dr Neil Kad, from the University of Kent, added: "This Parkinson's UK funded work shows how investment in basic science can open up new ways of studying and ultimately treating neurodegenerative disease."

Dr Arthur Roach, Director of Research and Development at Parkinson's UK, said: "It's a difficult task to develop treatments that can stop the toxic build-up of proteins in the brains of people with Parkinson's. Supporting this kind of innovative research approach is starting to make imaginable today what seemed impossible a decade ago.

"We need more successes, like this one, if we are to develop drugs that could actually slow or stop the progression of Parkinson's. At the moment no drugs are capable of doing this."

The researchers designed the 10 amino-acid peptide by screening a library of peptides based on the region of α-synuclein that is mutated in patients with early onset Parkinson's. This is the first time that this part of the α-synuclein protein has been explored as a potential drug target.

The researchers next hope to test the peptide in mammalian neurone cells and then develop it into a drug that is effective in humans.
-end-
For further information, please contact Alison Jones in the University of Bath Press Office on +44 (0)1225 386 986 or +44 (0)7917 870 134.

Notes

Harish Cheruvara, Victoria L. Allen-Baume, Neil M. Kad and Jody M. Mason
"Intracellular screening of a peptide library to derive a potent peptide inhibitor of α-synuclein aggregation" is published online in the Journal of Biological Chemistry
http://www.jbc.org/content/early/2015/01/23/jbc.M114.620484

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Parkinson's UK

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