With its elegant double helix and voluminous genetic script, DNA has become the of darling of nucleic acids. Yet, it is not all powerful. In order for DNA to realize its potential — for genes to become proteins — it must first be transcribed into RNA, a delicate molecule that requires intense care and guidance.
“Gene expression is a lot more complicated than turning on a switch,” says Robert B. Darnell, the Robert and Harriet Heilbrunn Professor. “There’s a whole layer of regulation that alters both the quality and quantity of a protein that’s produced from a gene. And much of it happens at the level of RNA.”
In the brain, RNA’s job as a gene tuner is vital to ensuring that the right proteins are made at the right time; and when this process go awry, the consequences can be serious. Darnell’s lab recently found that the brain’s response to stroke depends on the precise regulation of a subtype of RNA; and they have also learned that mutations affecting gene regulation underlie some cases of autism spectrum disorder.
A new study by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) has identified a chemical “switch” that controls both the generation of new neurons from neural stem cells and the survival of existing nerve cells in the brain. The switch that shuts off the signals that promote neuron production 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 chemical switch, MEF2, may be a potential therapeutic target to protect against neuronal loss in a variety of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and autism.
“We have shown that when nitric oxide (NO) — a highly reactive free radical — reacts with MEF2, MEF2 can no longer bind to and activate the genes that drive neurogenesis and neuronal survival,” said Stuart Lipton, M.D., Ph.D., director and professor in the Neuroscience and Aging Research Center at Sanford-Burnham, and a practicing clinical neurologist. “What’s unique here is that a single alteration to MEF2 controls two distinct events — the generation of new neurons and the survival of existing neurons,” added Lipton, who is senior author of the study.
The pattern of brain alterations may be similar in several different neurodegenerative diseases, which opens the door to alternative therapeutic strategies to tackle these diseases.
Diseases of the central nervous system are a big burden to society. According to estimates, they cost €800 billion per year in Europe. And for most of them, there is no definitive cure. This is true, for example, for Parkinson disease. Although good treatments exist to manage its symptoms, they become more and more ineffective as the disease progresses. Now, the EU-funded REPLACES project, completed in 2013, which associated scientists with clinicians, has shed light on the abnormal working of a particular brain circuitry related to Parkinson’s disease. The results of the project suggest that these same circuits are implicated in different forms of pathologies. And this gives important insights into the possible common links between neurodegenerative diseases such as Parkinson and intellective disabilities or autism.