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【medical-news】亨廷顿病与大脑异常的胆固醇水平
Clues to mechanism of deadly movement disease
Mayo Clinic researchers have discovered a protein interaction that may explain how the deadly Huntington's disease affects the brain. The findings, published in and featured on the cover of the current issue of Human Molecular Genetics, show how the mutated Huntington's protein interacts with another protein to cause dramatic accumulation of cholesterol in the brain.
"Cholesterol is essential for promoting the connection network among brain cells and in maintaining their membrane integrity. Both the level of cholesterol and its delivery to the proper locations in the cell are essential for the survival of neurons," explains Mayo Clinic molecular biologist Cynthia McMurrary, Ph.D.
"Our discovery that the mutant Huntington's disease protein derails the cholesterol delivery system and causes cholesterol accumulation in neurons provides us with key results and solid clues to the mechanism of this disease," says Dr. McMurray. "Fully understanding the mechanism of toxicity is the key to developing treatments."
Huntington's disease -- sometimes called Huntington's chorea or St. Vitus' dance -- is a progressive, degenerative condition that causes nerve cells in the brain to waste away. Symptoms include uncontrolled movements, emotional disturbances and mental deterioration.
The mutant protein of Huntington's attacks the railroad system of brain cells and impairs transport of essential materials required for neurons to function. When this transportation system goes awry in the parts of the brain affected in Huntington's disease, motor skills, cognitive skills and even speech can be affected. A person cannot move without shaking, and physical control gradually deteriorates, often with accompanying personality changes, depression and increased risk of suicide. Those who have Huntington's commonly die from complications of the disease, such as falls or infections.
Approximately 30,000 Americans have Huntington's disease. Another 150,000 carry the gene and have a 50 percent risk of passing it on to their children. The disease is easily diagnosed by a blood test, but symptoms usually don't appear until middle age.
Significance of the Research
Their findings, say the researchers, provide the first direct link between the Huntington's protein and the protein that controls capture and trafficking inside the cell. Their research suggests a possible means by which Huntington's disease functions.
Because no one knows how the disease is incurred or spreads, this new information is critical and establishes a clear path for investigations to move forward.
The Mayo researchers observed the abnormal accumulation of cholesterol in cultured neuronal cells in the laboratory and in the brains of animal models. They found that this happens only when the mutant Huntington's protein is expressed together with the molecule, caveolin-1. Caveolin-1 is the major structural protein of small vesicles called caveolae, which capture cholesterol and move it in and out of the neuronal membranes. When the researchers "knocked out" expression of caveolin, the neurons expressing mutant Huntington's protein stopped
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Mouse control neuron (left) and neuron showing cholesterol accumulation in Huntington's disease.
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归队了 Mayo discovers link between Huntington's and abnormal cholesterol levels in brain
Clues to mechanism of deadly movement disease
Mayo发现亨廷顿病与大脑异常的胆固醇水平之间的关系
研究致命性运动疾病机理之线索
Mayo Clinic researchers have discovered a protein interaction that may explain how the deadly Huntington's disease affects the brain. The findings, published in and featured on the cover of the current issue of Human Molecular Genetics, show how the mutated Huntington's protein interacts with another protein to cause dramatic accumulation of cholesterol in the brain.
Mayo诊所的研究者发现一种蛋白质的相互作用能够解释致命性亨廷顿病如何累及大脑。这项研究证实，突变的亨廷顿蛋白与另一种蛋白相互作用，能够导致脑内胆固醇大量沉积。这项发现作为封面文章发表在最新一期的人类分子遗传学杂志上。
"Cholesterol is essential for promoting the connection network among brain cells and in maintaining their membrane integrity. Both the level of cholesterol and its delivery to the proper locations in the cell are essential for the survival of neurons," explains Mayo Clinic molecular biologist Cynthia McMurrary, Ph.D.
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作者:admin@医学,生命科学 2011-02-19 17:11
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