Navigation Links
Molecular cabal contributes to stroke damage

In the neural train wreck that is stroke, the cutoff of oxygen kills brain cells through a buildup of acid, as well as by overexciting receptors on the surface of brain cells. Now, researchers exploring the detailed mechanism of this excitotoxicity and acidotoxicity have discovered how an insidious chain of molecular events contributes to its damage. In an article in the November 23, 2005, issue of Neuron, Jun Gao and colleagues say that their findings could contribute to the development of drugs to protect against the molecular "cabal" that produces such lethality.

In their experiments, the researchers discovered the molecular mechanism linking two key components of neuronal damage due to oxygen starvation, or ischemia. One component is a type of receptor called an NMDA receptor (NMDAR). This receptor is triggered by glutamate, which is known to be released during ischemia.

The other component of neuronal damage that they studied is an "acid-sensing ion channel," (ASIC)--basically, a pore-like protein in the membranes of neurons. In response to the acid unleashed by ischemia, ASICs open to admit calcium into the cell, and calcium overload is central to neuronal death.

In their experiments, Gao and colleagues induced ischemia in rat brains, or deprived cultured neurons of oxygen, and analyzed the molecular effects. Their analyses revealed that such deprivation triggered NMDARs, which in turn activated an important cell switch called CaMKII. This enzyme, they found, acts on a particular ASIC, called ASIC1a, to greatly enhance its sensitivity to the acid induced by ischemia. This increased sensitivity causes the ASIC channel to open and flood the neuron with lethal doses of calcium.

Importantly, the researchers found in cultures of neurons that drugs that inhibited NMDAR or CaMKII prevented the ischemia-induced enhancement of ASIC sensitivity, as well as neuronal death.

"In summary, our report provides a functional linkage betwee n NMDAR-mediated exitotoxicity and ASIC-mediated acidotoxicity induced by ischemia, which is known to cause excessive glutamate release and acidosis. Both NMDARs and [calcium permeable] ASICs have now been implicated in ischemic neuronal damage.

"Our finding…sheds new light on the development of therapeutic agents against excitotoxic and acidotoxic neuronal damage," concluded the researchers. Also, they added, since such NMDARs and ASIC1a are involved in seizures and pain sensation, "a similar coupling between these two channels is likely to occur in these diseases as well."


'"/>

Source:Cell Press


Related biology news :

1. Molecular biology fills gaps in knowledge of bat evolution
2. Molecular machine may lead to new drugs to combat human diseases
3. Molecular Motors Cooperate In Moving Cellular Cargo, Study Shows
4. Molecular models advance the fight against malaria
5. Molecular fossils uncover link between viruses and the immune system
6. Molecular thermometers on skin cells detect heat and camphor
7. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
8. Molecular steps involved in the creation of gene-silencing microRNAs identified
9. Molecular miners find pain relief drugs from the sea
10. Molecular mechanism of feather formation found
11. Molecular trigger for Huntingtons disease found
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: