A protein called PARIS facilitates the most common form of Parkinson's disease (PD), Johns Hopkins scientists have discovered.
The findings could lead to important new targets for treatment.
Previous research has shown that a protein dubbed parkin protects brain cells by "tagging" certain toxic elements for natural destruction. Mutations in the parkin gene cause rare forms of PD that run in families, but its role remained unclear in sporadic late-onset PD, the prevalence of which is increasing as the population ages.
Using genetically alteredn mice as well as human brain tissue, the Hopkins team showed that another protein, PARIS, accumulates when the parkin gene is mutated and its protein degrading ability is blocked. Too much toxic PARIS tamps down the manufacture of a protective protein named PGC-1alpha. The less protection afforded to brain cells by this protein, the more they die and the greater the progression of PD.
"Of all the important changes that lead to the death of brain cells as a result of parkin inactivation, our studies show that PARIS is, without a doubt, a key player," said Ted Dawson, Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and scientific director of the Johns Hopkins Institute for Cell Engineering.
The findings the study has been published in Cell.