Two new studies have identified a mutation associated with an inherited form of Parkinson's disease (PD), which is a devastating incurable disease that leads to tremors and problems with movement and coordination.
The studies provide new insight into the pathogenesis of late-onset PD and present compelling evidence that implicates a novel protein-recycling pathway in neurodegeneration.
"Previous studies of familial parkinsonism have identified pathogenic mutations in several genes, providing mechanistic insight and novel targets for therapeutic intervention," the lead authors of one of the studies, Dr. Carles Vilarino-Guell and Dr. Matthew J. Farrer from the University of British Columbia, said.
"In our study, we identified a pathogenic mutation associated with PD in a Swiss family where multiple individuals presented with disease.
"Confirmation of the discovery was an international effort embraced by neurologists in Canada, Israel, Norway, Switzerland, Taiwan, Tunisia, and the United States," they stated.
A second independent study, led by Dr. Tim M. Strom from the Institute of Human Genetics in Neuherberg, Germany and Dr. Alexander Zimprich from the Medical University of Vienna, used the same sophisticated sequencing techniques to look for causal mutations in a family from Austria with multiple incidences of late-onset PD.
Both groups discovered the same mutation in the vacuolar protein-sorting-associated protein 35 (VPS35) gene in affected family members.
The VPS35 protein is part of a complex called the "retromer" that mediates the intracellular transport and sorting of membrane-associated cell-surface proteins that are going to be recycled or destroyed.
"A single variant in the VPS35 gene was found in all affected family members investigated, was absent in general population samples, and was detected in two additional PD families," Dr. Strom and Dr. Zimprich said.
Taken together, the findings suggest that the VPS35 mutation is the genetic determinant of the late-onset PD examined in the studies and that perturbation of retromer-mediated protein sorting is linked with neurodegeneration.
Cell Press has published the study in the July 9 issue of The American Journal of Human Genetics.