Single change in protein could boost Parkinson's risk

Washington, Feb 27 : Researchers at University of Florida Genetics Institute have found that a single change in a protein, commonly found in the brain, could be the deciding factor in whether or not a person develops Parkinson.

Parkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech.

Scientists have discovered that alpha-synuclein protein found in brain cells can be lethal if its amino acid structure lacks a chemical compound called a phosphate.

Alpha-synuclein is said to help brain cells communicate but mutations in the protein may play a crucial role in the development of neurological diseases.

"We have another potential target for therapy, but there is a great deal left to discover," said Nicholas Muzyczka, Ph.D., a professor of molecular genetics and microbiology in the College of Medicine and an eminent scholar with the UF Genetics Institute.

"This is one more piece of information about what might be causing the toxicity in Parkinson's disease, and it gives us a little more to go on about what alpha-synuclein does in the brain," he added.

"We know of several enzymes that can cause phosphorylation in the proper position of the alpha-synuclein protein," said Oleg Gorbatyuk, Ph.D., an assistant professor of molecular genetics and microbiology.

"Increasing their expression in brains afflicted with Parkinson's disease could possibly provide a gene therapy approach to the disease," he added.

The experiments were conducted using a rat model where the researchers used gene transfer to enhance the production of three versions of alpha-synuclein in particular region of the rats' brains. The other side was not treated, for comparison purposes.

Of the types of alpha-synuclein, the one that simulated phosphorylation at position 129 of the protein was nontoxic. But the other versions of the protein all caused significant loss of dopamine neurons in the substantia nigra.

The findings appear in Proceedings of the National Academy of Sciences.

ANI