An explanation as to why exposure to the metal manganese is a risk factor for Parkinson's disease, is put forward in a study published online in Nature Genetics.
Parkinson's disease is a neurodegenerative disorder characterized by the loss of neurons that produce dopamine, a key neurotransmitter, resulting in tremor, rigidity and related symptoms. Previous work has identified several genes that are mutated in some cases of Parkinson's disease, but their connection to each other has been obscure.
Susan Lindquist and colleagues show in yeast cells that the toxicity caused by one Parkinson's disease-associated protein, alpha-synuclein, can be suppressed by coexpression of another, ATP13A2, suggesting that they have related functions. The authors also observe this genetic interaction in cultured rat neurons. ATP13A2 is predicted to be a metal transporter, and the team show that yeast cells lacking the gene are more sensitive to manganese.
As manganese exposure is a known risk factor for Parkinson's disease, this work raises the possibility that individuals with mutations in the genes encoding ATP13A2, alpha-synuclein or others in this pathway may be particularly sensitive to manganese toxicity.
Susan Lindquist (Whitehead Institute for Biomedical Research, Cambridge, MA, USA)
Abstract available online.
(C) Nature Genetics press release.
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