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Team finds promising new drug target for Alzheimer's disease
Date:4/20/2010

CHAMPAIGN, lll. Researchers at the University of Illinois have identified a potential drug target for the treatment of Alzheimer's disease: a receptor that is embedded in the membrane of neurons and other cells.

A protein fragment associated with Alzheimer's disease activates this receptor, sparking increased activity in the affected neurons, eventually leading to cell death, the researchers report. The new findings appear in the FASEB Journal.

Scientists have known for decades that a protein fragment, called amyloid-beta (AM-uh-loyd BAIT-uh), is a key to the riddle of Alzheimer's disease. Alois Alzheimer himself first found aggregates of this "peculiar substance" in the brain of a dementia patient after her death. These bundles of protein, or plaques, are composed almost entirely of amyloid-beta, and still are used to diagnose Alzheimer's disease after death.

Animals with amyloid plaques in the brain experience a decline in brain function that mirrors that of Alzheimer's disease. A recent study found that neurons closest to these plaques tend to be hyperexcitable relative to normal, while activity in the surrounding neurons is depressed, indicating an imbalance in brain activity associated with these plaques.

Other studies have found that clumps of only two, or a few, amyloid-beta fragments somehow stimulate a receptor, called the AMPA receptor. When amyloid-beta binds to a neuron, the AMPA receptor opens a channel that lets calcium or sodium ions into the cell.

Normally the AMPA receptor opens this channel only when it binds to glutamate, a potent neurotransmitter that is important to normal brain function as well as memory and learning. In either case, the quick influx of ions causes a nerve impulse.

To date, scientists have not been able to identify a mechanism by which amyloid-beta causes the AMPA receptor channel to open, however.

"If a mouse is exposed to amyloid-beta in the brain, it
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Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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