Fragile X syndrome (FXS) is caused by transcriptional silencing in neurons of the FMR1 gene product, fragile X mental retardation protein (FMRP), a repressor of dendritic mRNA translation. The lack of FMRP leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, a disorder that currently has no effective therapeutics. Fragile X mice were treated with chronic bryostatin-1, a relatively selective protein kinase Cε activator. Long-term treatment rescued adult fragile X mice from the disorder phenotypes, including normalization of most FXS abnormalities in hippocampal brain–derived neurotrophic factor expression and secretion, postsynaptic density-95 levels, glycogen synthase kinase-3β phosphorylation, transformation of immature dendritic spines to mature synapses, densities of the presynaptic and postsynaptic membranes, and spatial learning and memory.
See article at J Pharmacol Exp Ther 2014, 349:393–401.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics