Stabilizing the ties that bind a protein important in Parkinson’s disease to its buddies might help fend off the disease, a new study of the protein’s structure suggests.
Alpha-synuclein builds up in tough aggregates in the brains of patients with Parkinson’s disease. Researchers thought that this protein was normally a floppy, snakelike molecule.
But now, neuroscientist and neurologist Dennis Selkoe of Brigham and Women’s Hospital and Harvard Medical School and his colleagues show that alpha-synuclein normally forms bands of four molecules in living cells. These quartets (scientists call them tetramers) of alpha-synuclein molecules resist the clumping that leads single molecules of the protein down the path to brain cell destruction, Selkoe and colleagues report online August 14 in Nature.
Discovering that alpha-synuclein works in groups of four could be important in treating or preventing Parkinson’s disease, says Patrik Brundin, a neuroscientist at Lund University in Sweden. The findings suggest that loner alpha-synuclein molecules could be “part of the ‘bad guy’ pathway, and stabilizing it as a tetramer might help avoid the disease,” he says.
No one yet knows whether quartets of alpha-synuclein disintegrate into single molecules in the brains of people with Parkinson’s disease, leading to big brain-cell-killing plaques. Studies comparing normally aging brains with those of people with the disease may help answer those and other questions raised by the study, Brundin says.