Independent research teams from Harvard Medical School and Children’s Hospital Boston have identified a master protein that sheds light on one of neurobiology’s biggest mysteries--how neurons change as a result of individual experiences. The research, which appears in two papers in the latest issue of Science (Feb 17), identifies a central protein that regulates the growth and pruning of neurons throughout life in response to environmental stimuli. This protein, and the molecular pathway it guides, could help investigators understand the process of learning and memory, as well as lead to new therapies for diseases in which synapses either fail to form or run rampant, such as autism, neurodegenerative diseases, and psychiatric disorders.
Though axons and dendrites can be easily spotted waxing and waning under the microscope, the molecular middlemen working inside the cell to shape the neuron’s sinewy processes have been much more elusive. The teams found a protein that works in the nucleus of neurons that either pares down or promotes synapses depending on whether or not the neuron is being activated. The protein, myocyte enhancer factor 2 (MEF2), turns on and off genes that control dendritic remodeling. In addition, one of the teams has identified how MEF2 switches from one program to the other, that is, from dendrite-promoting to dendrite-pruning, and the researchers have identified some of MEF2’s targets.
The uncovering of the MEF2 pathway and its genetic switch helps fill in a theoretical blank in neurobiology, but what excites the researchers are the potential implications for the clinic. "Changes in the morphology of synapses could turn out to be very important in a whole host of diseases including neurodegenerative as well as psychiatric disorders," said Azad Bonni, MD, PhD, HMS Associate Professor of Pathology who, with colleagues, authored one of the papers. Michael Greenberg, PhD, HMS Professor of Neurology at Children’s Hospital Boston, who led the other team, believes that the MEF2 pathway could play a role in autism and other neurodevelopmental diseases.
The birth of a new protein
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