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alpha-synuclein

Asthma medicine

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I had asthma as a child, and I still occasionally develop mild wheezing from exercising in cold air or catching a bad cold. I keep an inhaler on hand for those occasions, as this is a quick and effective way to deliver a medication that opens up those constricted airways. Now, an NIH-supported team has made the surprising discovery that some asthma medicines may also hold the potential to treat or help prevent Parkinson’s disease, a chronic, progressive movement disorder that affects at least a half-million Americans.

The results, published recently in the journal Science, provide yet another example of the tremendous potential of testing drugs originally intended for treating one disease for possible use in others [1]. In this particular instance, researchers screened a library of more than 1,100 well-characterized chemical compounds—including drugs approved by the Food and Drug Administration for treating asthma—to see if they showed any activity against a molecular mechanism known to be involved in Parkinson’s disease.

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Untreated yeast shows clumps of brightly colored spots, while treated yeast are more even in their color.

Caption: Left, yeast sick with too much α-synuclein, a protein that is implicated in Parkinson’s disease. Right, the same yeast cells after a dose of NAB, which seems to reverse the toxic effects of α-synuclein.
Credit: Daniel Tardiff, Whitehead Institute

Many progressive neurodegenerative disorders like Alzheimer’s, Huntington’s, and Parkinson’s disease, are characterized by abnormal clumps of proteins that clog up the cell and disrupt normal cellular functions. But it’s difficult to study these complex disease processes directly in the brain—so NIH-funded researchers, led by a team at the Whitehead Institute for Biomedical Research, Cambridge, MA, have turned to yeast for help.

Now, it may sound odd to study a brain disease in yeast, a microorganism long used in baking and brewing. After all, the brain is made up of billions of cells of many different types, while yeast grows as a single cell. But because the processes of protein production are generally conserved from yeast to humans, we can use this infinitely simpler organism to figure out what the proteins clumps are doing and test various drug candidates to halt the damage.

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Photos of a healthy brain cell and a brain cell affected by Parkinson's

Caption: (LEFT) A healthy neuron with the alpha-synuclein (green) protein diffusely spread in the cell. The bright reddish dots are the garbage disposal lysosomes with alpha-synuclein entering, which gives them an orange hue. (RIGHT) This is a sick neuron from a LRRK2 brain. The lysosomes are enlarged and puffy because the alpha-synuclein is stuck outside and unable to enter the trash.
Credit: Samantha Orenstein and Dr. Esperanza Arias, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York

I’m blogging today to tell you about a new NIH funded report [1] describing a possible cause of Parkinson’s disease: a clog in the protein disposal system.

You probably already know something about Parkinson’s disease. Many of us know individuals who have been stricken, and actor Michael J. Fox, who suffers from it, has done a great job talking about and spreading awareness of it. Parkinson’s is a progressive neurodegenerative condition in which the dopamine-producing cells in the brain region called the substantia nigra begin to sicken and die. These cells are critical for controlling movement; their death causes shaking, difficulty moving, and the characteristic slow gait. Patients can have trouble swallowing, chewing, and speaking. As the disease progresses, cognitive and behavioral problems take hold—depression, personality shifts, sleep disturbances.

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