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:4/19/2016)... 20, 2016 The new GEZE ... compact web-based "all-in-one" system solution for all door components. ... or the door interface with integration authorization management system, ... systems. The minimal dimensions of the access control and ... building installations offer considerable freedom of design with regard ...
(Date:4/13/2016)... CHICAGO , April 13, 2016  IMPOWER physicians ... are setting a new clinical standard in telehealth ... By leveraging the higi platform, IMPOWER patients can ... weight, pulse and body mass index, and, when they ... quick and convenient visit to a local retail location ...
(Date:3/23/2016)... Massachusetts , March 23, 2016 /PRNewswire/ ... im Interesse erhöhter Sicherheit Gesichts- und Stimmerkennung ... Xura, Inc. (NASDAQ: MESG ), ... bekannt, dass das Unternehmen mit SpeechPro zusammenarbeitet, ... aus der Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016 A person commits ... the crime scene to track the criminal down. ... U.S. Food and Drug Administration (FDA) uses DNA evidence to ... Sound far-fetched? It,s not. The FDA has ... to support investigations of foodborne illnesses. Put as simply as ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published today in ... patient who developed lymphedema after being treated for breast cancer benefitted from an injection ... for dealing with this debilitating, frequent side effect of cancer treatment. , ...
(Date:6/23/2016)... 2016 On Wednesday, June 22, 2016, ... 0.22%; the Dow Jones Industrial Average edged 0.27% lower to ... down 0.17%. Stock-Callers.com has initiated coverage on the following equities: ... (NASDAQ: NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... BIND ). Learn more about these stocks by accessing their ...
Breaking Biology Technology: