During Fragile X Syndrome (FXS), there is damage to protein synthesis operations and actin dynamics. In this new study, a team of neuroscientists from New York University and Katholic University has devised an intervention that normalizes those broken biological functions. The work was published yesterday and can be found in Science Signaling.
According to the scientists, it's been established that FXS is due to the silencing of the FMR1 genes. The silencing leads to a loss of the expression of fragile X mental retardation protein (FMRP), which suppresses protein synthesis. Without this suppressor, protein synthesis doesn't get turned off, producing a range of mental and physical disorders.
The lack of FMRP increases the functionality of eIF4E, which is required to initiate protein synthesis. It also disrupts the activity of a protein called CYFIP1, which regulates eIF4E, actin dynamics and dendrite structures.
So the researchers used a drug called 4EGI-1 in mice with FXS syndrome. The saw that it blocked the interactions between eIF4E and a specific protein, eIF4G, a critical partner in initiating protein synthesis. This caused eIF4E to bind to CYFIP1, which reduces protein synthesis as well as a pathway that regulates actin dynamics.
"Our findings are consistent with the idea that an imbalance of protein synthesis and actin dynamics contribute to physiological problems in FXS mice," explains New York University Professor Eric Klann, senior author of the study. "Moreover, they offer a potential approach to treating individuals with Fragile X syndrome: targeting a specific protein, eIF4E, that regulates protein synthesis."
Image: An abnormal dendrite of a neuron from FXS mice. Image courtesy of Francesco Longo, NYU's Center for Neural Science.