The inherited forms are marked by alterations, or mutations, in one of two different proteins, parkin or alpha-synuclein (aS), but how they might lead to the same disorder isn't well understood. One answer, the Hopkins scientists report, is that both proteins interact with a third protein, synphilin, and the mutations disturb this interaction.
While it is still not known how this disturbance might result in the death of certain nerve cells that characterizes PD, the common thread offers clues for further studies, says Ted Dawson, M.D., Ph.D, of the Johns Hopkins School of Medicine.
"We were trying to see if the genetic mutations converge with what's known about the non-inherited disease, as is the case for Alzheimer's disease," explains Dawson, professor of neurology and neuroscience and director of the Program in Neural Regeneration and Repair for the Johns Hopkins Institute for Cell Engineering. "And now, all roads in Parkinson's disease seem to lead to alpha-synuclein."
The study was funded by the United States Public Health Service and the Edward T. and Anna Mitchell Family Foundation.
In Parkinson's disease, nerve cells that produce a chemical called dopamine die, starving the brain of a crucial messenger. Many of these dead and dying nerve cells contain protein blobs that include parkin, aS and synphilin. Understanding the formation of these clumps, called Lewy bodies, might eventually help identify targets for new treatments, Dawson says.
To begin with, the study sheds some light on how these three proteins normally interact. Parkin was already known to mark certain proteins for destruction by recruiting a fourth protein called ubiquitin. Synphilin was only known to bind to aS, wh
Contact: Joanna Downer
Johns Hopkins Medical Institutions