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Genetic Mechanisms in Blood Cells Play a Vital Role in Curbing Parkinson's Disease

by Hannah Punitha on July 22, 2008 at 7:33 PM
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 Genetic Mechanisms in Blood Cells Play a Vital Role in Curbing Parkinson's Disease

An international team of scientists have found that genetic mechanisms in blood cells play a crucial role in controlling a gene and protein that causes Parkinson's disease.

Patients with Parkinson's disease (PD) have elevated levels of the protein called alpha-synuclein in their brains. As the protein clumps, or aggregates, the resulting toxicity causes the death of neurons that produce the brain chemical dopamine.

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Consequently, nerves and muscles that control movement and coordination are destroyed.

They found that the activity of three genes that control the synthesis of heme, the major component of hemoglobin that allows red blood cells to carry oxygen, matched the activity of the alpha-synuclein gene.
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GATA-1 protein, which turns on the blood-related genes, was also a major switch for alpha-synuclein expression, and it induced a significant increase in alpha-synuclein protein.

In addition, related protein, GATA-2, was expressed in PD-vulnerable brain cells was also found to directly control alpha-synuclein production.

"Understanding how GATA factors work in the brain may provide fundamental insights into the biology of Parkinson's disease," said Emery Bresnick, a UW-Madison professor of pharmacology who is an expert on GATA factors and their functions in blood.

Researchers hope that new findings may allow scientists to design therapies that keep alpha-synuclein levels within the normal range.

"Simply lowering alpha-synuclein levels by 40 percent may be enough to treat some forms of Parkinson's disease," said Dr. Clemens Scherzer of Harvard.

"So far, researchers have focused on ways to get rid of too much 'bad' alpha-synuclein in Parkinson patients' brains. Now we will be able to tackle the problem from the production site, and search for new therapies that lower alpha-synuclein production up front," he added.

The family of GATA factors consists of six members, and some of them, beyond GATA-2, may also be influencing alpha-synuclein expression in the brain.

"Identifying these would further add to the complexity of regulating the production of the 'bad player' in Parkinson's disease," said Dr. Michael Schlossmacher from University of Ottawa.

The study is published in the Proceedings of the National Academy of Sciences.

Source: ANI
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