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Iron-moving malfunction may underlie neurodegenerative diseases, aging
Date:9/22/2008

ANN ARBOR, Mich.---A glitch in the ability to move iron around in cells may underlie a disease known as Type IV mucolipidosis (ML4) and the suite of symptoms---mental retardation, poor vision and diminished motor abilities---that accompany it, new research at the University of Michigan shows.

The same deficit also may be involved in aging and neurodegenerative diseases such as Alzheimer's and Parkinson's, says lead author Haoxing Xu, an assistant professor of molecular, cellular and developmental biology.

The findings are scheduled to be published online Sept. 14 in the journal Nature.

An interest in iron transport led Xu to investigate ML4, another symptom of which is iron-deficiency anemia. Perhaps, he and his collaborators reasoned, impaired iron transport could explain both the anemia and the other problems that go hand-in-hand with ML4, a genetic disorder that mainly affects Jews of Eastern European background. Children with ML4 begin showing signs of developmental delay and eye problems during the first year of life and typically fail to progress beyond the level of a 15-month-old. Although the disease is rare, recent discovery of some children with milder forms of the condition raises the possibility of additional mild, undiagnosed cases.

To explore the possible role of iron transport in the disease, Xu's group focused on a protein called TRPML1. A mutation in the gene that produces TRPML1 is known to cause ML4, so the protein seemed like a logical starting point for investigating mechanisms responsible for the disease, even though TRPML1 had never been shown to be involved in iron transport. The only protein with that distinction was DMT1, which facilitates iron uptake in the gut and in cells that will become red blood cells, but not in most other cell types.

"Essentially all cells, including nerve cells and muscle cells, need iron," Xu said. "We wondered what happens in those cells where DMT1 isn
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Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

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