Link Between Parkinson's Gene, Red Blood Cell Production Revealed
New research published in the Proceedings of the National Academy of Sciences reveals a key link between a gene involved in Parkinson’s disease and genes that regulate iron metabolism during red blood cell production, thus opening up a potential avenue for developing new therapies. The discovery results from a collaboration between Ottawa scientist Dr. Michael Schlossmacher and colleagues in the United States.
Patients with Parkinson’s have high levels of a protein called alpha-synuclein in their brain cells. As the protein clumps, or aggregates, the resulting toxicity causes select nerve cells to die, disabling the control of muscle movement and posture. High levels of iron are also found in the same brain areas of patients with Parkinson’s disease, but until now, there has been no explanation to link the two.
Dr. Schlossmacher and his collaborators made the surprising discovery that the alpha-synuclein gene was expressed at high levels in red blood cells as well as in brain cells. Follow-up experiments revealed that alpha-synuclein was regulated together with a series of genes that help red blood cells use iron to carry oxygen throughout the body, and that production of all of these genes was turned on simultaneously by a factor called GATA-1. Further experiments revealed that a related family member, called GATA-2, was responsible for regulating the alpha-synuclein gene in brain cells.
“Our findings are important because they provide a unique window into how alpha-synuclein is made in nerve cells of the brain,” said Dr. Schlossmacher. “Genetic evidence has suggested that if we could reduce alpha-synuclein levels even modestly in Parkinson’s patients, we would be able to make a real impact. A potential therapy based on that discovery would be many years away, but this is a first step in the right direction. This research is also important because it provides the first possible link between alpha-synuclein and iron, two hallmark findings in Parkinson’s disease.”
Dr. Schlossmacher holds the Canada Research Chair in Parkinson’s disease at the Ottawa Health Research Institute and the University of Ottawa (Faculty of Medicine), and is a neurologist at The Ottawa Hospital. This research was conducted in partnership with Dr. Emery Bresnick of the University of Wisconsin School of Medicine and Public Health and Dr. Clemens Scherzer of Harvard Medical School. It was funded by the Michael J. Fox Foundation, the National Institutes of Health, the American Federation for Aging Research and the M.E. and M.O. Hoffman Foundation.
Dr. Schlossmacher is a member of Ottawa’s Parkinson Research Consortium, which is supported by the Parkinson Society Ottawa, The Ottawa Hospital Foundation and many generous individuals in the community. Parkinson's affects at least 100,000 Canadians with the number of cases expected to at least double by the year 2050.