MEF2 gene: A potential therapeutic target for protecting neuronal loss in Alzheimer's disease, Parkinson -
A new study by researchers from the Research Institute Sanford-Burnham medical (Sanford-Burnham) has identified a "switch" chemical that controls both the generation of new neurons from neural stem cells and survival of nerve cells in the existing brain. The switch that cuts the signals that promote the production of neurons and survival is in abundance in the brains of Alzheimer's patients and stroke victims. The study, published July 3 in cell reports , suggests that the chemical switch, MEF2, may be a potential therapeutic target to protect against neuronal loss in various neurodegenerative diseases such as Alzheimer ' Alzheimer, Parkinson and autism.
"We showed that when nitric oxide (nO) -a highly reactive free radical reacts with MEF2, MEF2 can no longer bind and activate genes that lead neurogenesis and neuronal survival" said Stuart Lipton, MD, Ph.D., Director and Professor in neuroscience and aging Research Center at Sanford-Burnham, and a clinical neurologist practicing. "What is unique here is that a single change in both MEF2 control separate events: generation of new neurons and survival of existing neurons, "said Lipton, who is the lead author of the study
in the brain, the transcription factors are critical for binding. external stimuli in the production of proteins, which allows to adapt to changing environments neurons. the family members MEF2 transcription factors were found to play an important role in neurogenesis and neuronal survival, as well as learning and memory processes. And MEF2 gene mutations have been associated with a variety of neurodegenerative diseases, including Alzheimer's disease and autism.
The process of NO-protein modifications-known as S-nitrosylation-name has been first described by Lipton and colleagues some 20 years ago. S-nitrosylation has important regulatory functions in normal physiological conditions in the body. However, with aging, environmental toxins, or stress-related injuries, abnormal S-nitrosylation reactions may occur, which contributes to the pathogenesis of the disease.
"Our laboratory had already shown that S-nitrosylation of MEF2 controlled neuronal survival in Parkinson's disease," said Lipton. "Now we have shown that this reaction is even more ubiquitous, occurring in other neurological conditions such as stroke and Alzheimer's disease. While the main MEF2 target genes may be different in various diseases and areas the brain, the remarkable new discovery here is that we may be able to address each of these neurological disorders by preventing a change S-nitrosylation common to MEF2.
"the results suggest that the development of a small therapeutic molecule-one that can cross the blood-brain barrier and S-nitrosylation of MEF2 block or otherwise increase MEF2 transcriptional activity could promote new growth of brain cells and protect cells existing in many diseases neurodegenerative, "said Lipton.
"We've already found several of these molecules in our screening and drug discovery broadband efforts, so that the new drug development potential to attack this way is very exciting," said Lipton .
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