Small changes in a protein linked to Parkinson’s disease may have a significant impact on the development of the condition, researchers say.
The team, based at Cambridge University, UK, examined the protein alpha-synuclein. Tiny changes in the sequence of alpha-synuclein can affect microscopic processes in the brain, potentially resulting in Parkinson’s, they say.
The protein consists of 140 amino acids which normally aid the smooth flow of chemical signals within the brain. But it sometimes malfunctions, folding in the incorrect way and creating amyloid fibrils. These protein deposits are called Lewy-bodies in Parkinson’s disease.
Lead researcher, PhD student Patrick Flagmeier, and colleagues tested mutated forms of alpha-synuclein found in people from families with a history of Parkinson’s disease. He reports that just one change to the protein’s amino acid sequence can create mutations.
Such small changes can have a profound effect on how quickly or slowly fibrils start to form, say the team in Monday’s (29 August) Proceedings of the National Academy of Sciences.
Furthermore, the mutations can cause fibrils to break off and form more deposits elsewhere in the brain.
"As a finding, it helps us to understand fundamental things about the system by which this disease emerges," says Flagmeier. "In the end, if we can understand all of this better, that can help us to develop therapeutic strategies to confront it. Our hope is that this study will contribute to the global effort towards comprehending why people with these mutations get the disease more frequently, or at a younger age."
He adds that Parkinson’s disease can still develop in people who do not have mutated forms of alpha-synuclein.
Flagmeier, P. et al. Mutations associated with familial Parkinson’s disease alter the initiation and amplification steps of a-synuclein aggregation. Proceedings of the National Academy of Sciences 29 August 2016
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