Researchers have known that mutations in a key gene called parkin are a major cause of Parkinson’s disease (PD). Now they have discovered a new mechanism by which the parkin gene can be compromised, a finding that they say could lead to new drugs for the disorder.
Andrea Lozano, Senior Scientist at the Toronto Western Research Institute, of University Health Network and Professor of Surgery at the University of Toronto and colleagues found that the protein produced by a gene called BAG5 inhibits parkin activity and the action of another protein, called Hsp70, a "chaperone" that works with parkin. They found in studies with rats that BAG5 enhances the death of the dopaminergic neurons targeted by Parkinson’s and that inhibiting the gene reduces such death.
Parkin is part of the cell’s "garbage disposal" system that rids the cell of unwanted proteins by degrading them. Mutations of parkin eliminate its ability to chemically "tag" such proteins to designate them for destruction in the cell’s proteasome--a process called ubiquitinylation. Loss of such ability causes such protein garbage to aggregate into lethal clumps in neurons--a hallmark of many neurodegenerative diseases. In the brain, the parkin protein works with Hsp70, which helps correct the folding of misfolded proteins.
Heidi Hardman | EurekAlert!
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