In a breakthrough that may eventually lead to new ways to treat Parkinson’s disease, two independent research groups have found that a gene linked to inherited Parkinson’s works by disabling a cell’s mitochondria.
Mitochondria are the power centers of the cells. They are structures within cells that provide the energy a cell needs to move, divide and produce proteins.
In earlier studies, researchers had found that inherited Parkinson’s is caused by mutations in the PTEN-induced putative kinase 1 (PINK1) gene.
Parkinson’s disease is a progressive disorder caused by degeneration of nerve cells in the part of the brain that controls movement. First described as "the shaking palsy" in 1817, it affects an estimated 500,000 Americans, with 50,000 new cases reported each year. It is the second most common neurodegenerative disease; only Alzheimer’s strikes more people.
The two reports appear in the May 3 online issue of Nature.
Both research teams showed that flies without a functional PINK1 gene have defects in mitochondria that trigger muscle problems and, according to one team, degeneration of neurons that produce dopamine.
In addition, both research groups show that the PINK1 protein acts upstream of Parkin, another protein linked to the sporadic forms of Parkinson’s. These two proteins appear to act in a common pathway involved in maintaining mitochondrial function.
"We found that when you remove PINK 1, the animals are alive, but they have defects in mitochondria," said lead author of the first report Dr. Ming Guo, an assistant professor of neurology at UCLA. "In addition, we found that Parkin and PINK 1 function in the same pathway," she added.
In the second report, Korean researchers had similar findings.
"Our study, using Drosophila [fruit fly] model, revealed that two distinct gene products, Parkin and PINK1, converge in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopamine neurons," said lead researcher Jongkyeong Chung, an associate professor in the Department of Biological Sciences at the Korea Advanced Institute of Science and Technology. "This clearly suggests that mitochondrial failure is the central mechanism in the pathogenesis of Parkinson’s disease."
"Our findings indicate that there may be a specific molecular target in the PINK1-Parkin pathway," Chung said. "We believe that identification of this target will bring significant insight into basic and clinical science to develop effective drugs for Parkinson’s disease."
There may be clinical implications to this finding, Guo confirmed. "If we understand how the disease is brought on, it will help us develop more therapies," she added. "If we can find drugs that can rescue these mitochondrial functions, that would be a much better drug than the current therapies that are targeted on dopamine replacement."
However, one expert doesn’t think these findings will have any implications for treatment in the near future.
"These findings probably won’t have any immediate impact on treatment," said Dr. Jon Stoessl, director of the Pacific Parkinson’s Research Center at the University of British Columbia, in Canada. "You can never be sure there will be a direct therapeutic link in studies done in animal models."
"Because people have already suggested that mitochondrial function is important in Parkinson’s, this is not going to suggest a novel approach to treatment, but it will strengthen the importance of searching for treatments along these lines," Stoessl added.
