Navigation Links
New understanding about mechanism for cell death after stroke leads to possible therapy
Date:11/22/2009

Scientists at the Brain Research Centre, a partnership of the University of British Columbia Faculty of Medicine and Vancouver Coastal Health Research Institute, have uncovered new information about the mechanism by which brain cells die following a stroke, as well as a possible way to mitigate that damage. The results of the study were recently published online in Nature Medicine.

Following a stroke, many brain cells continue to die even after blood flow has been restored. Researchers have long known this is due to a complicated cascade of cellular messages that lead to the "self-destruction" and death of brain cells.

The team of Brain Research Centre scientists discovered that, in animal models, the over-activation of NMDA receptorsspecial receptors on the surface of brain cellsactivates another protein, called SREBP-1, which subsequently causes cell death. SREBP-1 is found naturally in cells throughout the body and is involved with cholesterol and other fat production.

NMDA receptors control the movement of calcium in and out of brain cells, which is necessary for normal brain function. However, following a stroke, levels of glutamatethe most abundant chemical messenger in the brainrise rapidly in cells, leading to over-activation of NMDA receptors, an excess of calcium entering cells, and the onset of cell death.

The researchers found that under normal conditions, SREBP-1 is largely kept in an inactive form by a protein known as Insig-1. After a stroke, over-activation of NMDA receptors leads to a rapid degradation of Insig-1, which increases the level of active form of SREBP-1.

"How over-activation of NMDA receptors caused cell death after a stroke has been a mystery," says Dr. Yu Tian Wang, co-lead on the study, a Professor in the UBC Division of Neurology, and the Heart and Stroke Foundation of BC & Yukon Chair in Stroke Research. "We found that SREBP-1 was one of the missing key players in that process."

While the detailed mechanisms by which activation of SREBP-1 leads to brain cell death remain to be established, the researchers discovered a way to inhibit SREBP-1 and thereby significantly reduce cell death.

"We developed a drug that can stabilize Insig-1, which in turn inhibits the activity of SREBP-1," says Dr. Max Cynader, co-lead on the study, a Canada Research Chair in Brain Development, and the Director of the Brain Research Centre. "By doing so, we were able to prevent cell death."

The researchers also found that the drug works post-stroke in animal models. "When we administered it post-stroke, there was less brain cell damage 30 days later than compared to controls," says Dr. Wang. "This is important because previous studies focused on blocking the NMDA receptors in order to prevent cell death, but this approach didn't work because it affected normal cell function and had a relatively short therapeutic window. The drug we studied works downstream of NMDA receptors and appears to have less detrimental side effects with a much improved therapeutic window."

Further investigations will help researchers understand how SREBP-1 causes cell death and to further determine efficacy of the drug. As well, because of the protein's connection to cholesterol synthesis and other cellular functions, further investigations may reveal if it has a role in other neurological disorders, such as ALS, and whether the drug might be effective for those conditions as well.


'/>"/>

Contact: Melissa Ashman
mashman@brain.ubc.ca
604-827-3396
University of British Columbia
Source:Eurekalert

Related biology news :

1. A study by the MUHC and McGill University opens a new door to understanding cancer
2. Understanding hypertension in African Americans proves elusive
3. Systems Biology poised to revolutionize the understanding of cell function and disease
4. Gregory Hannon wins 2007 Paul Marks Prize for contributions to understanding and treating cancer
5. Understanding, combating foodborne pathogens E. coli 0157 and salmonella
6. Researchers discover important tool in understanding differentiation in human embryonic stem cells
7. Atmospheric measuring device for understanding smog formation
8. Researchers move 2 steps closer to understanding genetic underpinnings of autism
9. Scientists expand understanding of how river carbon impacts the Arctic Ocean
10. From delicious to death: Understanding taste
11. USP Convention and Chinese Pharmacopoeia Commission sign Memorandum of Understanding
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based and ... 2022", published by MarketsandMarkets, the market is expected to be worth USD 18.98 ... Continue Reading ... ...      ...
(Date:3/22/2017)... , March 21, 2017 ... Cloud used by retailers such as 1-800-Flowers and ... platform — Product Recommendations and Replenishment. Using Optimove,s machine ... more personalized product and replenishment recommendations to their ... also on predictions of customer intent drawn from ...
(Date:3/20/2017)... ALLENTOWN, Pa. , March 20, 2017 ... PD 2.0 personal spirometer and Wellness Management System (WMS), ... Founded in 2010, PMD Healthcare is a ... Company with a mission dedicated to creating innovative solutions ... of life. With that intent focus, PMD developed the ...
Breaking Biology News(10 mins):
(Date:6/20/2017)... ... June 20, 2017 , ... Biologist Dawn Maslar MS has found a ... book, Men Chase, Women Choose: The Neuroscience of Meeting, Dating, Losing Your Mind, and ... on men. ”The logical next step, in my estimation, was to scientifically track the ...
(Date:6/20/2017)... ... June 20, 2017 , ... ... a well-versed leader with extensive assay development and biomarker expertise, as VP of ... a Boston CRO specializing in bio-analytical assay development and sample testing services. The ...
(Date:6/19/2017)... ... June 19, 2017 , ... ... service activities supporting EDETEK’s products including training, implementation, support, and client process and ... new role. He has previously held leadership roles for service providers and top-tier ...
(Date:6/19/2017)... ... June 19, 2017 , ... A colony of healthy honey bees is ... by delivering pollen and nectar containing nutrients necessary for growth and survival. Better nutrition ... Many recent indicators point to a decline in honey bee health. Sick and weakened ...
Breaking Biology Technology: