Parkinson's Clues

Parkinsons drugs to prevent alpha synuclein from unfolding

(RxWiki News) Parkinson's disease is complex and not completely understood. A misunderstanding about a key protein may suggest other approaches would be more successful in treating the disease.

The finding challenges existing information available about the disease, and could aid with new diagnostic blood tests.

"Talk to a neurologist about new Parkinson's disease tests."

Dennis Selkoe, senior author and the Vincent and Stella Coates Professor of Neurologic Diseases at Brigham and Women’s Hospital and Harvard Medical School, said data shows that protein alpha-synuclein was essentially miscategorized as an unfolded protein without structure.

In healthy cells, however, the protein appears to have a radically different structure. Selkoe said the discovery is important to understanding how the protein functions and how it becomes altered in Parkinson's.

Proteins usually fold into a three dimensional structure comprised of chemical building blocks. The arrangement of the folds is dictated by the protein's behavior and properties.

Scientists have long believed that alpha-synuclein, which forms clumps in Parkinson's patients, formed a randomly-coiled chain in healthy cells. However, a recent study found it is more orderly and complex. It also is not unfolded as previously believed.

This is key as pharmaceutical companies have worked to target drugs to prevent alpha-synuclein from unfolding since it was believed to be folded.

Researchers gently probed the protein, wondering if rough handling may have caused properties to have been overlooked.  They were surprised to find single, isolated forms of alpha-synuclein. Using gels and other methods. investigators conducted additional experiments, which showed that twists in the protein were orderly.

Additional understanding about the protein could aid researchers with the possibility of being able to prevent continued degeneration from Parkinson's and related diseases. It also could provide a new method for diagnostic blood, serum or spinal fluid tests to identify disease stage.

The research was published in journal Nature.

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Review Date: 
August 16, 2011