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:6/18/2019)... ... June 18, 2019 , ... Cosmetic Town, ... the world of cosmetic facial rejuvenation in June. The Cosmetic Town website will ... experienced in performing various methods of cosmetic facial rejuvenation and videos that take ...
(Date:6/18/2019)... ... June 18, 2019 , ... ... needs in the field of urology, today announced that Aaron Berger, MD, Associated ... of Excellence. The designation recognizes that Dr. Aaron Berger has achieved a high ...
(Date:6/16/2019)... ... June 14, 2019 , ... ... today announced it has received the coveted “2019 Best DLP Solution Provider” Award ... Platform along with the latest additions to its Data Security Portfolio (DSP) during ...
(Date:6/16/2019)... ... ... Convoy of Hope continues to celebrate its 25th anniversary. Since its founding ... the world. To date, Convoy has worked with more than 46,000 partners to serve ... without the dedication and generosity of churches, organizations, and individuals who believe in their ...
(Date:6/14/2019)... ... 14, 2019 , ... United Breast Cancer Foundation ... Saturday, July 13th. UBCF is thrilled to return to the “City of Brotherly ... This second event was added after an overwhelming response to the Tempur-Pedic® Mattress ...
Breaking Medicine News(10 mins):
(Date:6/16/2019)... , ... June 15, 2019 , ... ... 1.4% of the global population. The condition is characterized by damage to ... complications including thyroid disease, anemia, osteoporosis, fertility problems and some cancers, to name ...
(Date:6/13/2019)... ... 13, 2019 , ... The Centers for Medicare & Medicaid ... Improvement and Innovation Contractor. This designation will allow NQIICs to bid on Task ... with other Quality Improvement contractors under the new CMS Indefinite Delivery/Indefinite Quantity (IDIQ) ...
(Date:6/13/2019)... ... June 13, 2019 , ... The American Psychiatric Nurses Association announced today ... executive director Nicholas Croce Jr., MS. The search will be led by an APNA ... APNA Presidents, and Council and Chapter leaders. , The job description and more information ...
Breaking Medicine Technology: