Rebalancing protein synthesis in fragile X syndrome

Fragile X Syndrome: A Disorder of Synaptic Protein Synthesis Dynamics

| Fragile X syndrome (FXS) is a developmental disorder resulting from trinucleoide repeat expansion in the 5’UTR of FMR1 gene. Cognitive deficiency and autistic features are among the common phenotypes of FXS. FMR1 gene codes for the protein FMRP, the absence of which leads to abnormal dendritic spine morphology and defective synaptic plasticity in animal models of fragile X syndrome. FMRP is a...

Synaptic regulation of protein synthesis and the fragile X protein.

Protein synthesis occurs in neuronal dendrites, often near synapses. Polyribosomal aggregates often appear in dendritic spines, particularly during development. Polyribosomal aggregates in spines increase during experience-dependent synaptogenesis, e.g., in rats in a complex environment. Some protein synthesis appears to be regulated directly by synaptic activity. We use "synaptoneurosomes," a ...

Altered cerebral protein synthesis in fragile X syndrome: studies in human subjects and knockout mice.

Dysregulated protein synthesis is thought to be a core phenotype of fragile X syndrome (FXS). In a mouse model (Fmr1 knockout (KO)) of FXS, rates of cerebral protein synthesis (rCPS) are increased in selective brain regions. We hypothesized that rCPS are also increased in FXS subjects. We measured rCPS with the L-[1-(11)C]leucine positron emission tomography (PET) method in whole brain and 10 r...

The fragile X syndrome.

We have begun to appreciate that the extent of this disorder is much wider than merely mental retardation. It is also a common cause of learning and emotional problems in mildly affected female carriers with normal IQs. These children present an enormous challenge to all child-care providers, be they in medicine, education, or in various therapy disciplines. Early identification is essential, a...

Fragile X syndrome.