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Iron-storing disorders shed light on Parkinson's

Iron-storing disorders shed light on Parkinson's



NEW YORK, Jul 23 (Reuters Health) - Researchers have uncovered genetic defects underlying two rare disorders in which iron builds up in brain cells, resulting in deteriorating brain function.

The findings may help researchers understand more common disorders, such as Parkinson's, Huntington's and Alzheimer's disease, which also involve increased levels of iron in brain cells, researchers say.

The two studies were reported July 23 in an online publication of Nature Genetics. In the first study, Dr. John Burn from the Institute of Human Genetics, Newcastle upon Tyne, UK, and his colleagues identified a genetic mutation that resulted in patients having symptoms similar to those of people with Huntington's or Parkinson's disease.

The symptoms of the disorder, called adult-onset basal ganglia disease, include involuntary movements, spasticity and rigidity, and typically strike patients between 40 to 55 years of age. However, the patients do not show a decline in reasoning ability.

Burn's team examined genetic material from five patients with the disorder and compared it with that of three healthy people. The investigators found that all of the affected individuals had a defective version of an iron-storing protein, which could cause iron to accumulate in brain cells.

In the second paper, Dr. Susan J. Hayflick from the Oregon Health and Science University in Portland, and colleagues describe their discovery of the genetic defect underlying a rare disorder called Hallervorden-Spatz syndrome (HSS). These patients, numbering about 100 in the US, also suffer severe damaging effects from a buildup of iron in their brain cells.

"People with Parkinson's disease have increases of iron in their brain in some of the same areas in which it is increased in HSS," Hayflick told Reuters Health. "We are speculating that some variation in this gene (that causes HSS) may be at the basis of the common forms of Parkinson's disease," she said.

"We are actually looking now at a group of Parkinson's patients to see if there are changes in this gene," Hayflick said. "We don't think this gene is going to be the cause of all Parkinson's disease, but it may be a significant contributor," she said.

According to Hayflick, the iron buildup is caused by a mutated protein that is unable to break down a B vitamin called pantothenic acid, or vitamin B5. This defect, through a chain of events, may trigger the accumulation of iron, she said.

Hayflick did not want to speculate on whether taking pantothenic acid as a vitamin supplement may help or hinder HSS or Parkinson's, but she said, "we are working to develop compounds (based on pantothenic acid) that would be able to get into cells in order to treat the disorder(s)."

SOURCE: Nature Genetics July 23, 2001.

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