p38beta MAPK not critical to brain inflammation, study finds
(Medical Xpress)—A study by a leading Alzheimer's researcher at the University of Kentucky provides new evidence that will help researchers home in on the molecular mechanisms involved in inflammation of the central nervous system (CNS) and aid drug-development strategies for treating inflammatory neurological diseases.
The research was led by Linda Van Eldik, director of UK's Sanders-Brown Center on Aging, and included co-authors Bin Xing and Adam Bachstetter from the Van Eldik lab. The study demonstrated that the beta isoform of p38 mitogen-activated protein kinase (MAPK) has no apparent effect on inflammatory cytokine response and neurotoxicity in brain-cell cultures or in the brains of living mice.
Others have reported that the p38beta isoform is not involved in peripheral inflammatory disorders, such as arthritis and inflammatory bowel disease. However, whether p38beta is important in brain inflammation had not been studied before.
Taken together with previous studies by Van Eldik's lab, which document the critical role of p38alpha in CNS proinflammatory cytokine production and neuron survival, the new study further supports the idea that p38alpha, and not p38beta, is the key p38 isoform involved in central inflammatory responses.
The new findings also suggest that development of p38-inhibitor drugs to target CNS inflammatory diseases may not need to consider retention of p38beta inhibitory activity, but should instead focus on selectively targeting the p38alpha MAPK isoform as a potential therapeutic strategy.
The study used mice where the p38beta kinase was specifically eliminated, and asked whether brain cells that did not have p38beta could generate an inflammatory cytokine response and induce subsequent neuron death after treatment with a standard inflammatory stimulus.
The research found that in brain-cell cultures, and in mice treated with the inflammatory stimulus, the inflammatory cytokine response and neurotoxicity were the same whether the mice had normal p38beta levels or were deficient in p38beta. These results showed that, in agreement with peripheral inflammation models, p38beta is also expendable in the brain in terms of regulation of proinflammatory cytokines and downstream neurotoxicity.
Van Eldik's paper, "Deficiency in p38beta MAPK Fails to Inhibit Cytokine Production or Protect Neurons against Inflammatory Insult in In Vitro and In Vivo Mouse Models," appeared online Feb. 15 in PLOS One, a peer-reviewed, open-access journal published by Public Library of Science.
Journal reference: PLoS ONE
Provided by University of Kentucky
- New publication examines effect of early drug administration on Alzheimer's animal model Jul 24, 2012 | not rated yet | 0
- New tactic for controlling blood sugar in diabetes contradicts current view of the disease Sep 04, 2011 | not rated yet | 0
- New pathway involved in rheumatoid arthritis identified Apr 13, 2010 | not rated yet | 0
- The Japanese traditional therapy, honokiol, blocks key protein in inflammatory brain damage Mar 19, 2012 | not rated yet | 0
- New drug could treat Alzheimer's, multiple sclerosis and brain injury Jul 24, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
2 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
23 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions ...
Medical research 13 hours ago | 5 / 5 (2) | 0
The human gut is loaded with commensal bacteria – "good" microbes that, among other functions, help the body digest food. The gastrointestinal tract contains literally trillions of such cells, and yet the ...
Medical research 17 hours ago | 5 / 5 (3) | 0 |
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
Medical research 17 hours ago | 4.9 / 5 (9) | 1 |
On May 22, JoVE will publish details of a technique to measure the health of human genetic material in relation to a patient's age. The method is demonstrated by the laboratory of Dr. Gil Atzmon at New York's Albert Einste ...
Medical research 21 hours ago | not rated yet | 0
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
Medical research 22 hours ago | not rated yet | 0 |
US teen births have dropped to a record low, but the country still has one of the highest rates among developed nations, the US Centers for Disease Control and Prevention said Thursday.
22 minutes ago | not rated yet | 0
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
17 hours ago | 4.7 / 5 (3) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
14 hours ago | 5 / 5 (2) | 2 |
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
6 hours ago | not rated yet | 0
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
14 hours ago | 4 / 5 (2) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
15 hours ago | not rated yet | 0 |