A protein key to Parkinson's disease has likely been mischaracterized as a natively unfolded protein that lacked structure, a new study has discovered.
The protein, alpha-synuclein, appears to have a radically different structure in healthy cells than previously thought, challenging existing disease paradigms and suggesting a new therapeutic approach.
"Our data show that alpha-synuclein was essentially mistakenly characterized as a natively unfolded protein that lacked structure," said Dennis Selkoe, the Vincent and Stella Coates Professor of Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School and senior author of the study.
"We think this discovery has fundamental importance for understanding both how alpha-synuclein normally functions and how it becomes altered in Parkinson's," he added.
Scientists have long assumed that alpha-synuclein occurs in healthy cells as a single, randomly-coiled chain that resembles a writhing snake. Selkoe's team has proven, however, that the structure is far more orderly and sophisticated.
"This will open some new therapeutic doors," said first author Tim Bartels, a postdoctoral researcher in Selkoe's lab.
"Everybody thought the protein was unfolded, so pharmaceutical companies have focused on preventing unfolded alpha-synuclein from aggregating," he stated.
He recommends a new strategy-keeping the folded form of the protein stable.
The finding was published online August 14 in the journal Nature.