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:4/18/2017)...  Socionext Inc., a global expert in SoC-based imaging and computing ... M820, which features the company,s hybrid codec technology. A demonstration utilizing ... Inc., will be showcased during the upcoming Medtec Japan at Tokyo ... Las Vegas Convention Center April 24-27. ... Click here for an image ...
(Date:4/11/2017)... GARDENS, Fla. , April 11, 2017 /PRNewswire/ ... management and secure authentication solutions, today announced that ... by Intelligence Advanced Research Projects Activity (IARPA) to ... IARPA,s Thor program. "Innovation has been ... and IARPA,s Thor program will allow us to ...
(Date:4/6/2017)... LONDON , April 6, 2017 ... Control, RFID, ANPR, Document Readers, by End-Use (Transportation & ... Energy Facility, Oil, Gas & Fossil Generation Facility, Nuclear ... Healthcare, Educational, Other) Are you looking for ... Authentication sector? ...
Breaking Biology News(10 mins):
(Date:4/28/2017)... (PRWEB) , ... April 28, 2017 , ... ... research organization (CRO) has validated a 0.2 ng/mL lower limit (LLOQ) assay for ... a 0.5 ng/mL LLOQ assay, the ultra-low trace nicotine assay meets additional needs ...
(Date:4/27/2017)... ... April 27, 2017 , ... Mitotech S.A, a Luxembourg ... Hereditary Optic Neuropathy (LHON) patients. LHON is a rare devastating genetic disease that leads ... eye drops in a group of 20 patients carrying 11778, 14484 and 3460 mutations ...
(Date:4/27/2017)... ... April 27, 2017 , ... ... flow controllers based on capillary thermal mass flow technology provide exponentially more accurate ... applications. Over 80% of all industrial processes—such as those involving chemical reactions, ...
(Date:4/27/2017)...  Pendant Biosciences, Inc. (formerly Nanoferix, Inc.), a privately-held ... delivery technologies, today announced that it has been accepted ... Toronto . Shawn Glinter , ... "We are excited to become part of the JLABS ... honored to be the first Tennessee ...
Breaking Biology Technology: