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Molecule that spurs cell's recycling center may help Alzheimer's patients
Date:3/16/2011

Yuan Tian, a postdoctoral fellow in Greengard's lab, tested various compounds for their ability to reduce the buildup of amyloid-beta by exposing cultured cells to compounds known to activate autophagy. They then compared the effect of these compounds by removing growth factors from the culture medium, a well-established stimulant of autophagy known as "starvation."

The researchers found that SMER28 was the most effective compound, and focused their studies on it to characterize the cellular components involved in this phenomenon. They compared the effect of SMER28 on amyloid-beta formation using normal cells or cells where the expression of genes known to be involved in autophagy was reduced or abolished. They found that three important autophagic players were involved, and one of them was essential for SMER28's effect.

Identifying a cure for Alzheimer's disease remains a major challenge. Four drugs are currently approved by the Food and Drug Administration to treat Alzheimer patients. Unfortunately none of these drugs halt progression of the disease and their impact on cognitive defects are minimal. On top of that, current strategies are associated with severe side effects. This limitation was highlighted recently by failures in various clinical trials.

"Our work demonstrates that small molecules can be developed as therapies, by activating a cellular function called autophagy, to prevent Alzheimer's disease," says Flajolet. "By increasing our understanding of autophagy, it might be possible to stimulate it, pharmacologically or naturally, to improve the quality of life for aging people."

The results also suggest the power of diet to prevent damage to neurons. It has been known that a low calorie diet is beneficial for longer life expectancy as well as for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. "Our results suggest that a low calorie diet might lead to a higher autophagy activity that
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
Source:Eurekalert

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