Navigation Links
OHSU scientists advance understanding of brain receptor; may help fight neurological disorders
Date:5/28/2013

PORTLAND, Ore. For several years, the pharmaceutical industry has tried to develop drugs that target a specific neurotransmitter receptor in the brain, the NMDA receptor. This receptor is present on almost every neuron in the human brain and is involved in learning and memory. NMDA receptors also have been implicated in several neurological and psychiatric conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia and depression.

But drug companies have had little success developing clinically effective drugs that target this receptor.

Now, researchers at Oregon Health & Science University's Vollum Institute believe they may understand why. And what they've discovered may help in the development of new therapies for these conditions.

In a paper published in the current issue of the Journal of Neuroscience, OHSU scientists describe their work on NMDA receptors. There are various types of NMDA receptors, resulting from differences in the protein components that make up the receptor. These differences in the protein components produce receptors with varying properties.

As drug companies have worked to develop compounds that manipulate the activity of these receptors, the focus of much of this drug discovery effort has been on a specific NMDA receptor subtype. In their Journal of Neuroscience paper, the OHSU scientists describe their discovery that the specific receptor subtype that drug companies have seen as a target is an almost nonexistent contributor of NMDA receptor action.

What does exist, the OHSU scientists found, was a different kind of NMDA receptor subtype one containing two specific protein components, called GluN2A and GluN2B. NMDA receptors containing these two components were not thought to be very common. The OHSU study found that not only was this NMDA receptor subtype more common than previously believed, it was the most common subtype at synapses. And it was far more common than the receptor subtype that has been the target of drug development efforts.

"What our paper shows is that one reason no drugs have worked well to this point may be because that particular NMDA receptor subtype isn't there in high quantities. The target they've been looking for isn't the target that's there," said Ken Tovar, Ph.D., a senior postdoctoral fellow at the Vollum Institute. Tovar's co-authors on the paper were Gary Westbrook, M.D., senior scientist and co-director of the Vollum Institute, and Matthew McGinley, Ph.D., a former graduate student in the Westbrook laboratory.

Tovar said these findings could provide a new target for drug development.

"If you know what's there, then you know what to go after you just have to figure out how to do it," Tovar said.

The OHSU study also provides clues into how the function of this most common NMDA receptor subtype might be manipulated. Highly specific drugs interact with either GluN2A or GluN2B. Tovar and colleagues demonstrated that when GluN2A and GluN2B coexist in the same receptor, molecules that targeted GluN2A change the behavior of the receptor in ways that could be clinically beneficial.

"NMDA receptors have been implicated in a diverse list of neurological and psychiatric conditions. Thus, the more we know about how to modulate the behavior of the receptors that are there at synapses the greater chance we have of finding drugs to treat these conditions," Tovar said.

"From the perspective of drug development, knowing the nature of your target is one way to keep drug development costs down," said Tovar. "Spending resources investigating a target that turns out to be unimportant means those costs get passed on to the drugs that are effective."


'/>"/>

Contact: Todd Murphy
murphyt@ohsu.edu
503-494-8231
Oregon Health & Science University
Source:Eurekalert

Related biology news :

1. Should I stay or should I go? CSHL scientists link brain cell types to behavior
2. Scientists discover the origin of a giant synapse
3. A majority on Earth face severe self-inflicted water woes within 2 generations: Scientists
4. UCLA life scientists present new insights on climate change and species interactions
5. Scientists sequence genome of sacred lotus, which likely holds anti-aging secrets
6. Scientists confirm that the Justinianic Plague was caused by the bacterium Yersinia pestis
7. Salk scientists find potential therapeutic target for Cushings disease
8. American Chemical Society resource connects scientists, discoveries, chemistry & biology interface
9. Scientists alarmed by rapid spread of Brown Streak Disease in cassava
10. Scientists discover how brains auditory center transmits information for decisions, actions
11. Scientists discover new way protein degradation is regulated
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/15/2016)... Germany , December 15, 2016 ... provider, today announced an agreement with NuData Security, an ... forces. The partnership will enable clients to focus on good ... local data protection regulation. ... In order to provide a one-stop fraud ...
(Date:12/15/2016)... Mich. , Dec. 15, 2016  There is ... car doors or starting the engine. Continental will demonstrate ... Las Vegas . Through the combination ... Start and Entry) and biometric elements, the international technology ... of vehicle personalization and authentication. "The integration ...
(Date:12/8/2016)... Dec. 8, 2016  Singulex, Inc., the leader in ... entered into a license and supply agreement with Thermo ... agreement provides Singulex access to Thermo Scientific BRAHMS PCT ... is used to diagnose systemic bacterial infection and ... to aid in assessing the risk of critically ...
Breaking Biology News(10 mins):
(Date:1/19/2017)...  ArmaGen, Inc., today announced that it has ... executive officer, as well as a member of ... more than 17 years of executive management experience ... and pharmaceuticals. "Mathias is a ... skillset necessary to lead ArmaGen to its next ...
(Date:1/19/2017)... ... January 19, 2017 , ... FireflySci Inc. is a go-getter ... The tremendous growth is accounted to two main factors. The first is the ... network of vendors supplying FireflySci products all around the world. , 2016 was a ...
(Date:1/19/2017)... , Jan. 18, 2017 Acupath Laboratories, ... announces the formation of an Executive Committee that will ... beyond. John Cucci , a 15-year ... from Director of Business Development to Chief Sales ... Mr. Cucci served in senior sales leadership roles at ...
(Date:1/18/2017)... Jan. 18, 2017   Boston Biomedical , an ... to target cancer stemness pathways, will feature data from ... at the 2017 ASCO Gastrointestinal Cancers Symposium, held from ... Napabucasin is an orally-administered investigational agent ... i Cancer stem cells (CSCs) possess the property ...
Breaking Biology Technology: