Navigation Links
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 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 researchers found, amyloid-beta binds to a different part of the receptor than that normally engaged by neurotransmitters and hormones. This means it may be possible to stop amyloid-beta from binding to it without hindering the other functions of the beta-2 adrenergic receptor.

Previous studies have shown that Alzheimer's patients who also take beta-blockers tend to see a slower decline in their mental function. These drugs are meant to treat hypertension and other conditions by targeting beta-adrenergic receptors, including beta-2. This finding provides further support to the idea that the beta-2 adrenergic receptor is a key to the ill effects of Alzheimer's disease.

Xiang and Cox stress that the beta-2 adrenergic receptor is almost certainly not the only important player in the damage that occurs in an Alzheimer's-afflicted brain. But they see it as a promising new potential target for future drug research.


'/>"/>

Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related medicine news :

1. Given No Chance to Survive with Pancreatic Cancer, Chicago Woman Finds New Life at Northwest Community Hospital
2. Study finds treatment-resistant ringworm prevalent among children in metro elementary schools
3. Convenience drives US women to buy over-the-counter contraception in Mexico, study finds
4. Dance therapy improves seniors gait, balance, researcher finds
5. The Medical Marijuana Industry Finds an Outside-the-Box Solution, "Inside the Box" With GrowOp Technology
6. Statins May Slow Progression of Multiple Sclerosis, New Study Finds
7. Study finds changes in fetal epigenetics throughout pregnancy
8. Statins may slow progression of multiple sclerosis, new study finds
9. Study Finds Military Prone to Infection With H1N1 Flu
10. Eating disorder cutoffs miss some of sickest patients, Stanford/Packard study finds
11. UBC graduate student finds a start/stop switch for retroviruses
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Team finds promising new drug target for Alzheimer's disease
(Date:2/10/2016)... ... 2016 , ... Ongoing news of the ravages of traumatic brain injury (TBI) ... survey that takes a closer look at cases of TBI being managed by their ... TBI among the aging population, and identifies the challenges associated with their care. , ...
(Date:2/10/2016)... , ... February 10, 2016 , ... ... organization, welcomes S.S. Nesbitt as the latest addition to its growing list of ... other locations throughout the Southeast, from Orlando to Huntsville and in between. , ...
(Date:2/10/2016)... ... ... AxoGen, Inc. (NASDAQ: AXGN), a leading medical technology company focused on the peripheral ... December 31, 2015 on Monday, February 29, 2016 after the market closes. , The ... release at 4:30 PM ET. Investors interested in participating by phone are invited to ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... award winner and inspirational speaker Jan Fox will serve as keynote speaker at ... will provide participants with tools to more effectively communicate with their own organizational ...
(Date:2/10/2016)... ... ... For additional information contact Phyllis Strupp 480-488-5858 , Brain improves with age, says ... to Brain Training" by award-winning author Phyllis Strupp explains how brain exercise ... 2016. A free review copy is available to the media at NetGalley . ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)... FARMINGDALE, N.Y., Feb. 9, 2016  Misonix, Inc. ... company that designs, manufactures and markets innovative therapeutic ... wound debridement, cosmetic surgery, laparoscopic surgery and other ... second quarter and the first half of fiscal ... --> --> Highlights ...
(Date:2/9/2016)... 2016  Unilife Corporation ("Unilife" or "Company") (NASDAQ: UNIS ... systems, today announced its financial results for the second quarter of ... Financial Results for the ... Revenue for the second quarter of fiscal ... period last year.  Cash receipts from customers for the second quarter ...
(Date:2/9/2016)... Pharmaceuticals plc (Nasdaq: JAZZ ) today announced that ... year financial results on Tuesday, February 23, 2016, after ... host a live audio webcast immediately following the announcement ... quarter and full year 2015 financial results and provide ... financial results. www.jazzpharmaceuticals.com .  Please connect to ...
Breaking Medicine Technology: