Navigation Links
New drug target for Alzheimer's, stroke is discovered by University at Buffalo scientists
Date:10/11/2011

BUFFALO, N.Y. -- A tiny piece of a critical receptor that fuels the brain and without which sentient beings cannot live has been discovered by University at Buffalo scientists as a promising new drug target for Alzheimer's and other neurodegenerative diseases.

The research on the NMDA (N-methyl-D-aspartate) receptor is being published online Oct. 11 in Nature Communications.

"This is the first time that this site has been shown to be useful as a drug target," says Gabriela K. Popescu, PhD, associate professor of biochemistry in UB's School of Medicine and Biomedical Sciences and senior author on the study.

"If we could find a drug that attaches itself to this site and locks together NMDA receptor subunits, that would be huge for fighting disability from stroke and Alzheimer's and other neurodegenerative diseases."

The research focuses on the brain's receptors for the neurotransmitter, glutamate, which is implicated in these diseases as well as in other conditions, such as glaucoma.

The two main glutamate receptors in the brain are NMDA and AMPA receptors, both of which play critical roles in human learning and memory. Both types of receptors are made of four subunits and within each receptor these subunits are organized in pairs called dimers.

Because these receptors are so similar in structure, Popescu explains, it was assumed that they function in much the same way.

"But when we altered the dimer interface, the site where two subunits come together within each pair, we found that the NMDA receptor works just the opposite of the way that the AMPA receptor works," Popescu explains. "Cementing this interface in AMPA receptors leads to more activity, whereas we found just the opposite to be true in NMDA receptors."

By locking the subunits together, the UB researchers were able to achieve a marked reduction in NMDA activity and, subsequently, a marked reduction in the amount of calcium that enters neurons in response to the neurotransmitter glutamate. Calcium overload due to overactive NMDA receptors is what eventually kills off neurons, Popescu explains, leading to the symptoms that occur after a stroke, and in Alzheimer's and other neurodegenerative diseases.

"The fact that by cross-linking the subunits, we could so dramatically reduce NMDA receptor activation demonstrates, for the first time, the tantalizing possibility that we may be able to develop new therapies that can much more effectively treat, or even one day prevent, some of these devastating diseases, like Alzheimer's and stroke," says Popescu.

And, because each type of NMDA receptor has a slightly different dimer interface, Popescu explains, this finding represents a new opportunity for rationally designing drugs that would preferentially inhibit only a select population of NMDA receptors in the brain, thus reducing the possibility of side effects.

Currently, the Alzheimer's drug called Namenda, one of the only existing pharmaceuticals that inhibit the NMDA receptor, targets a different site within the receptor.

"If a new drug could be developed to target the dimer interface, which we discovered to be inhibitory, it would allow more specific effects than current drugs," explains Popescu. "That's because at this particular interface, the interactions between these subunit interfaces are more precise than those currently being targeted."
'/>"/>

Contact: Ellen Goldbaum
goldbaum@buffalo.edu
716-645-4605
University at Buffalo
Source:Eurekalert

Related biology news :

1. Cleveland Clinic study discovers new targets for treating inflammatory, autoimmune diseases
2. Better planning required if EU is to meet energy targets
3. Targeting HIVs sugar coating
4. Protein found in heart may be target for colon cancer therapies
5. International study identifies new gene targets for hypertension treatment
6. Gladstone scientist finds new target for treating symptoms of Parkinsons disease
7. Researchers publish study on neuronal RNA targeting
8. A jumping genes preferred targets may influence genome evolution
9. Researchers identify new drug target that stimulates
10. Research offers new way to target shape-shifting proteins
11. Government-led efforts targeting eating habits of children needed to curb worldwide obesity epidemic
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/15/2016)... Puerto Rico , Jan. 15, 2016 ... big and small to find new ways to ensure ... culture. iOS and Android ... based on biometrics, transforming it into a hardware authorization ... that users swipe their fingerprint on their KodeKey enabled ...
(Date:1/11/2016)... 2016 Synaptics Incorporated (NASDAQ: SYNA ), ... that its ClearPad ® TouchView ™ 4300 ... separate categories in the 8 th Annual Mobile ... Breakthrough. The Synaptics ® TDDI solution enables faster ... thinner devices, brighter displays and borderless designs. ...
(Date:1/8/2016)... -- NXTD ), a company focused on ... privately held leading direct seller of vacation and entertainment ... company announced that on December 31, 2015, that WorldVentures ... to develop a proprietary new wireless smart card for ... unique smart wallet that serves to securely store all ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... 2016 Novan, Inc. today announced that Director Robert ... Directors of Novan. In addition, Robert Keegan has been ... Carolina . --> North Carolina ... received a total of $32.8 million of net proceeds in a ... network originating throughout the Research Triangle area of North ...
(Date:2/8/2016)... , Feb. 8, 2016  BioElectronics Corporation (OTC ... devices, announced today that it is responding to ... from the Securities and Exchange Commission posted on ... , Chairman of the Board of BioElectronics Corporation ... Business Administration at The Fuqua School of Business, ...
(Date:2/8/2016)... , ... February 08, 2016 , ... ... wide range of loose, bulk foods at various stages of the production process. ... used to inspect large bulk products post packaging such as sacks of dry ...
(Date:2/8/2016)... SHELTON, Conn. , Feb. 8, 2016  NanoViricides, Inc. (NYSE ... that its CEO, Eugene Seymour , MD, MPH, will present ... 5:30PM at the Waldorf-Astoria Hotel in New York City ... presentation will be in the Windsor Room at 5:30PM EST. Registered ... New York City . --> ...
Breaking Biology Technology: