Transcription factors are proteins that bind to specific DNA sequences, thereby controlling the flow of genetic information from DNA to RNA. One family of transcription factors, the nuclear factor kappa B (NF-kB) proteins, is known to play a central role in the cellular response to stress.
In a new study, researchers have identified a key player in the NF-kB stress response: the protein C-Rel. C-Rel forms a complex with another NF-kB protein, p50, and this complex is responsible for the stress-inducible transcription of a gene called CCL2.
The CCL2 gene encodes a chemokine, a protein that signals for the recruitment of inflammatory cells. In the new study, the researchers found that C-Rel-deficient mice showed a reduced stress-induced inflammatory response.
The findings suggest that C-Rel may be a potential target for the treatment of inflammatory diseases.
In the study, the researchers used a mouse model of stress that involves exposing the animals to cold water. They found that, compared to wild-type mice, C-Rel-deficient mice showed a reduced stress-induced production of CCL2.
The reduced production of CCL2 in C-Rel-deficient mice was associated with a decrease in the recruitment of inflammatory cells to the site of stress.
The findings suggest that C-Rel plays a key role in the stress-induced production of CCL2 and the ensuing inflammatory response.
The findings have implications for the treatment of inflammatory diseases. Inhibition of C-Rel may help to reduce the inflammatory response in these conditions.
Scientists have identified a key player in the cellular response to stress, a finding that could lead to new treatments for stress-related disorders such as depression, anxiety and post-traumatic stress disorder (PTSD).
The study, published in the journal Nature, shows that a protein called NR4A3 is essential for the proper functioning of a stress-response pathway in the brain.
Previous research has shown that this pathway is disrupted in people with stress-related disorders.
“Our findings suggest that NR4A3 could be a potential target for new treatments for stress-related disorders,” said study senior author Dr. Eric Nestler, the Marilyn M. Simpson Distinguished Chair in Neuroscience and co-director of the Center for Addictions, Personality and Mood Disorders at Icahn School of Medicine at Mount Sinai.
The study was conducted in mice, and the findings are likely to be applicable to humans.
NR4A3 is a protein that belongs to a family of proteins known as nuclear receptors. These proteins are involved in the regulation of gene expression.
NR4A3 is activated by stress, and it in turn activates a number of stress-responsive genes.
One of these genes encodes a protein called FKBP5, which is known to be involved in the stress response.
“We found that when NR4A3 is not working properly, FKBP5 is not expressed properly either,” said study first author Dr. Sofia D. Dzundza, a postdoctoral fellow in the Nestler lab.
“This is important because FKBP5 is thought to be a key player in the stress response.”
The findings could have implications for the development of new treatments for stress-related disorders.
“NR4A3 is a targetable protein, and our findings suggest that drugs that modulate NR4A3 activity could potentially be used to treat stress-related disorders,” Dr. Nestler said.
“This is a very exciting possibility, and we are currently working on developing such drugs.”
The study was conducted by scientists at Mount Sinai and Duke University.