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:

(Date:10/29/2015)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce that it has been ... one of only three finalists for a 2015 ... Growing" category. The Tekne Awards honor Minnesota ... innovation and leadership. iMedNet™ eClinical ...
(Date:10/29/2015)... OXFORD, Connecticut , October 29, 2015 /PRNewswire/ ... "Company"), a biometric authentication company focused on the ... Wocket® smart wallet announces that StackCommerce, a leading ... will be featuring the Wocket® smart wallet on ... NXTD ) ("NXT-ID" or the "Company"), a ...
(Date:10/26/2015)... 26, 2015 ... adds Biometrics Market Shares, Strategies ... well as Emerging Biometrics Technologies: Global ... its collection of IT and Telecommunications ... --> . ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica Richman and Zachary Apte, ... their initial angel funding process. Now, they are paying it forward to other ... stage investments in the microbiome space. In this, they join other successful ...
(Date:11/24/2015)... ... , ... The United States Golf Association (USGA) today announced Dr. Bruce Clarke, ... annually since 1961, the USGA Green Section Award recognizes an individual’s distinguished service to ... Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology in the department ...
(Date:11/24/2015)... Halozyme Therapeutics, Inc. (NASDAQ: HALO ) will be presenting at ... on Wednesday, December 2 at 9:30 a.m. ET/6:30 a.m. PT ... provide a corporate overview. th Annual Oppenheimer Healthcare ... ET/10:00 a.m. PT . Jim Mazzola , vice president ... --> th Annual Oppenheimer Healthcare Conference in ...
(Date:11/24/2015)... ... November 24, 2015 , ... Copper is an essential micronutrient ... to proteins, copper is also toxic to cells. With a $1.3 million award ... will conduct a systematic study of copper in the bacteria Pseudomonas aeruginosa (P. ...
Breaking Biology Technology: