says Peter King, M.D., and Burt Nabors, M.D., professors in the University of Alabama at Birmingham Department of Neurology.
The cytokines and chemokines secreted by the activated microglia and astrocytes in the brain or spinal column are IL1β, IL-6, TNF-α, iNOS, CXCL1, and CCL2. The messenger RNAs for those pro-inflammatory signaling proteins contain adenine- and uridine-rich elements, or AREs, that govern their expression.
Neuroinflammatory Mechanism
The study team has shown previously that HuR, an RNA regulator protein that binds to AREs, plays a major positive role in regulating the inflammatory cytokine production, making it a major control point in neuroinflammation.
The HuR translocates out of the nucleus of astrocytes in the acute CNS diseases spinal column injury and stroke. The team had shown that it translocates out of the nucleus in microglia in the chronic CNS disease ALS or amyotrophic lateral sclerosis.
Hence, these glial cells (microglia and astroglia cells) were found to rely on a key RNA-binding protein called HuR that protects the messenger RNAs encoding inflammatory mediators from degradation and promotes their translation into proteins.
In support of this, the study experiments were done in glial cell cultures and mice to open the door to the testing of their small molecule drug, SRI-42127 in models of acute and chronic neurological injury.
Novel Molecule – SRI-42127
It was found that treatment with SRI-42127 attenuated the triggers of neuroinflammation by reduced production of proinflammatory mediators, cytokines IL1β, IL-6, TNF-α, and iNOS, and the chemokines CXCL1 and CCL2.
Moreover, SRI-42127 also penetrated the blood-brain barrier to quickly suppress the neuroinflammatory responses.
“Our findings underscore HuR’s critical role in promoting glial activation and the potential for SRI-42127 and other HuR inhibitors to treat neurological diseases driven by this activation. This would be a non-opioid approach to treating pain,” say, King and Nabors.
Source: Medindia
For all the latest Health News Click Here
For the latest news and updates, follow us on Google News.
Denial of responsibility! NewsBit.us is an automatic aggregator around the global media. All the content are available free on Internet. We have just arranged it in one platform for educational purpose only. In each content, the hyperlink to the primary source is specified. All trademarks belong to their rightful owners, all materials to their authors. If you are the owner of the content and do not want us to publish your materials on our website, please contact us by email – [email protected]. The content will be deleted within 24 hours.
