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

impairs neuron function, causing memory deficits and behavioral deficits," said Kevin Xiang, a professor of molecular and integrative physiology at Illinois who led the new study with professor Charles Cox and postdoctoral fellows Dayong Wang and Govindaiah in the same department. "The question is how this peptide causes all these detrimental cellular effects."

For the new study, the researchers focused on the beta-2 adrenergic receptor, a protein that like the AMPA receptor resides in the cell membrane. Neurotransmitters and hormones normally activate the beta-2 adrenergic receptor, but amyloid-beta also induces a cascade of events in the neuron by activating the beta-2 adrenergic receptor, the researchers found. One of the downstream effects of this interaction is activation of the AMPA receptor ion channels. (In mice lacking the beta-2 adrenergic receptor, amyloid-beta had no discernible effect on AMPA receptors, they found.)

"We showed that we needed the presence of beta-2 adrenergic receptors to get the increase in the AMPA-mediated response," Cox said.

Further experiments showed that amyloid-beta does bind to the beta-2 adrenergic receptor.

Previous studies had found that blocking the AMPA receptor could alleviate the misfiring caused by amyloid plaques in the brain. But the AMPA receptor, which responds to glutamate, is important to learning and memory, so blocking it could also do harm, the researchers said.

"Glutamate is such a ubiquitous neurotransmitter throughout the brain, you can't simply go in and block its actions because if you do, you can just start rounding up the side effects," Cox said.

"Once you block the AMPA receptor you're basically dampening widespread neuronal excitability throughout the whole brain," Cox said. "Now we have something a bit more specific to latch onto: the beta-2 adrenergic receptor."

This receptor offers an attractive alternative target because, the researc
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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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