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Targeting Huntington’s, Parkinson’s from a Different Angle

March 9th, 2006 Medgadget Editors News

A new approach to therapeutic strategies against neurodegenerative diseases is being led by a team of investigators from MIT:

Huntington’s disease is caused by misfolded proteins, called huntingtin proteins, that aggregate and eventually form large clump-like “inclusions.” The disease is characterized by degeneration in the striatum, an area associated with motor and learning functions, and the cortex. The proteins may disrupt the function of cellular structures known as proteasomes, which perform a “trash can” function for the cell — disposing of cellular proteins that are misfolded or no longer needed, said Bodner [Ruth Bodner, a postdoctoral fellow in MIT’s Center for Cancer Research -ed.]
Without a functional proteasome, those cellular proteins accumulate, poisoning brain cells and impairing patients’ motor and cognitive function.
Until now, most researchers looking for Huntington’s treatments have focused on compounds that prevent or reverse the aggregation of huntingtin proteins. However, recent evidence suggests that the largest inclusions may not necessarily be harmful and could in fact be protective, said Bodner. So, the MIT and Harvard scientists decided to look for compounds that actually promote the formation of large inclusions.
The highest concentration of protein inclusions was found when the researchers applied a compound they called B2 to cells cultivated in the laboratory. The compound also had a strong protective effect against proteasome disruption, thus blocking one of the toxic effects of the huntingtin protein.
The B2 compound also promoted large inclusions and showed a protective effect in a cellular model of Parkinson’s disease, another neurodegenerative disorder caused by misfolded proteins.
In Parkinson’s disease, the mutant proteins destroy dopamine-producing cells in the substantia nigra. Normally, the dopamine transmits signals to the corpus striatum, allowing muscles to make smooth, controlled movements. When those dopamine-producing cells die, Parkinson’s patients exhibit the tremors that are characteristic of the disease.
The researchers are now working on finding a more potent version of the compound that could be tested in mice.

The press release…
Read more about this fascinating promising research in the latest article at MIT Technology Review…

Medgadget Editors

Medical technologies transform the world! Join us and see the progress in real time. At Medgadget, we report the latest technology news, interview leaders in the field, and file dispatches from medical events around the world since 2004.

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