Navigation Links
Unprecedented structural insights: NMDA receptors can be blocked to limit neurotoxicity
Date:1/22/2014

Cold Spring Harbor, NY Structural biologists at Cold Spring Harbor Laboratory (CSHL) and collaborators at Emory University have obtained important scientific results likely to advance efforts to develop new drugs targeting NMDA receptors in the brain.

NMDA (N-methyl D-aspartate) receptors are found on the surface of many nerve cells and are involved in signaling that is essential in basic brain functions including learning and memory formation. Problems with their function have been implicated in depression, schizophrenia, Alzheimer's and Parkinson's diseases, as well as brain damage caused by stroke.

Normally, NMDA receptors are activated by glutamate, the most common neurotransmitter of excitatory cell-to-cell messages in the brain.

Overactivation of NMDA receptors is a known cause of nerve-cell toxicity. Thus, drug developers have long sought compounds that can selectively block or antagonize NMDA receptors, while not affecting other types of glutamate receptors in the brain, whose function is essential. However, a basic question -- how those compounds bind and antagonize NMDA receptors -- has not been understood at the molecular level.

Over a period of years, CSHL Associate Professor Hiro Furukawa and colleagues have taken a step-by-step approach to learn about the precise shape of various subunits of the complex NMDA receptor protein, and demonstrating the relationship between different versions of the receptor's shape and its function. (see more here) Since the subunits have different biological roles, they have to be specifically targeted by drug compounds to obtain specific effects.

Furukawa's team has used a technique called x-ray crystallography to map various domains of the protein while it is bound to different chemical compounds, or antagonists, that downregulate its function. Today in the journal Neuron they publish the first crystal structures of two NMDA receptor subunits (called GluN1 and GluN2A) in complex with four different compounds known to have the capacity to inhibit, or antagonize, NMDA receptor function.

Showing this two-unit ligand binding domain (LBD) in complex with NMDA antagonists -- potential drugs -- reveals that each antagonist has a distinctive mode of binding the LBD. In essence, the "docking port" is held open, but to a different extent when different antagonists are bound. The study also reveals an element in the antagonist binding site that is only present in GluN2A subunit, but not in the others. This previously hidden information, says Furukawa, is critical: "It indicates different strategies to develop therapeutic compounds ones that bind to a certain type of NMDA receptors very specifically. Being able to target specific subtypes of the receptor is of enormous interest and has great therapeutic potential in a range of illnesses and injuries affecting the brain."


'/>"/>

Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert  

Related medicine news :

1. Unprecedented accuracy in locating brain electrical activity with new device
2. UT MD Anderson Cancer Center launches unprecedented Moon Shots Program
3. Ibrutinib has unprecedented impact on mantle cell lymphoma
4. Premium Astrology Client Care Team Offers Unprecedented 24-Hour Turnaround Time During March 2013 Reader's Appreciation Month
5. Unprecedented Plastic Surgery SEO Guarantee Announced by JD Media Surge, LLC
6. bioMérieux Partners with Ultimate Labs to Bring Unprecedented Speed to Pathogen Identification for Food, Drug, and Cosmetic Manufacturers
7. Gang members found to suffer unprecedented levels of psychiatric illness
8. Pacific Prime Clients with Aetna Receive Unprecedented Discounts on First Year Insurance Premiums
9. New Hawaiian Jellys “Slip…aaahs” Sandals Provide Unprecedented Comfort and Fashion for Flip Flop Enthusiasts
10. CARRE Foundation selects TGen for unprecedented research into causes of multiple system atrophy
11. An Unprecedented Initiative to Hit Cancer Head On
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Unprecedented structural insights: NMDA receptors can be blocked to limit neurotoxicity
(Date:5/4/2016)... ... May 04, 2016 , ... The preeminent surgical aftercare facility Pearl ... following breast cancer surgery. In March 2016, the 61-year-old model and reality TV star ... that occurs in the milk ducts, according to an interview with the Daily ...
(Date:5/4/2016)... ... 2016 , ... Warren L. Smith M.D. , There is a new tool ... people since the beginning of recorded medical history, and in spite of all the ... just a matter of inconvenience; bladder infections cost us billions of dollars annually in ...
(Date:5/4/2016)... ... May 04, 2016 , ... Over 40 athletic trainer’s (ATs) and athletic ... for the annual “Hike to Harrisburg” advocacy day. The annual lobbying effort is ... lobby Group. The goal for the day was to educate the elected legislators ...
(Date:5/3/2016)... ... May 04, 2016 , ... ... and global construction firms representing the Construction Industry Safety Initiative (CISI) and the ... one purpose: to inspire everyone in the industry to be leaders in safety. ...
(Date:5/3/2016)... (PRWEB) , ... May 03, 2016 , ... In April, ... with today’s latest technologies to help find the best steam and sauna solutions. , ... device, using responsive design. This improvement brings all of the site’s features, especially the ...
Breaking Medicine News(10 mins):
(Date:5/4/2016)... Research and Markets has ... Myeloma Market and Competitive Landscape Highlights - ...      (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ) , ... Highlights 2016, provides comprehensive insights into Multiple ... Myeloma market valuations and forecast, Multiple Myeloma ...
(Date:5/4/2016)... Research and Markets has ... Ischemic Stroke Market and Competitive Landscape Highlights ...      (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ) ... Market and Competitive Landscape Highlights 2016, provides ... products, Acute Ischemic Stroke epidemiology, Acute Ischemic ...
(Date:5/4/2016)... 4, 2016 Research ... "Global Acute Myeloid Leukemia Market and Competitive ... offering.       (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ... Market and Competitive Landscape Highlights 2016, provides ... products, Acute Myeloid Leukemia epidemiology, Acute Myeloid ...
Breaking Medicine Technology: