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Manganese poisoning is an environmental risk factor for a syndrome similar to Parkinson's disease and is prevalent in industries such as mining, welding and steel manufacturing. Exposure to high concentrations of manganese metal can have an effect on the central nervous system, triggering motion and dementia symptoms similar to Parkinson's disease.
In patients with Parkinson's disease, alpha-synuclein is often found to fold in the brain and form clumps. Kitler uses a model system for studying disease proteins, yeast cells, which also form clumps and die when the protein is expressed at high levels.
Kitler and others have long sought genes that prevent cell death caused by misfolding of α-synuclein in yeast, and Zui eventually found several genes. Animal experiments have shown that some of these (including a previously uncharacterized yeast gene YOR291W) protect neurons from the toxic effects of alpha-synuclein.
At the same time, European researchers reported that a type of early onset Parkinson's disease is caused by a mutation in the PARK9 gene. After screening yeast, Kitler confirmed that the YOR291W gene in yeast is close to the human PARK9 gene zui, which is a gene that can relieve the toxicity of α-synuclein. The findings suggest that Parkinson's disease genes can interact in unexpected ways.
Due to the similarity of the YOR291W gene to the PARK9 gene, Kitler et al. renamed it YPK9. Researchers at Purdue University and the University of Alabama and Kitler et al. have confirmed that the PARK9 gene also protects neurons from alpha-synuclein toxicity.
Later, the Kitler research team began to study the function of YPK9. They found that YPK9 encodes a metal transporter with a sequence similar to other known proteins that transport metals. The researchers deleted the yeast YPK9 gene and exposed it to various metals, such as zinc, copper, manganese, iron, etc. After zui, it was found that among all the metals tested, only YMn was present when manganese was present. Defective yeasts don't grow very well, they are allergic to manganese.
The researchers also found that proteins made from YPK9 are confined to the vacuole membrane of yeast cells, which are internal components of the cell that can be isolated for further processing. Accordingly, the researchers hypothesized that a vacuole is a bag of toxins in a cell that absorbs manganese and sequesters it to detoxify it away from other organelles. Once a mutation occurs in PARK9, it will cause dysfunction in the vacuolar detoxification process in yeast or humans.
American researchers found that Parkinson's disease is related to manganese poisoning
A team led by Dr. Oron Kittle, an assistant professor of cell and developmental biology at the University of Pennsylvania, recently discovered that there is something between Parkinson's disease and genetic causes. They found a genetic interaction between two Parkinson's disease genes (α-synuclein and PARK9) and determined that the PARK9 protein protects cells from manganese poisoning.