Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling
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چکیده
Lohith et al. (Mol Autism 4:15, 2013) recently identified increased metabotropic glutamate receptor 5 (mGluR5) expression in the frontal cortex (FC) of subjects with fragile X syndrome. These results are consistent with postmortem findings in cerebellar vermis and FC of subjects with autism (Fatemi and Folsom, Mol Autism 2:6, 2011; Fatemi et al. Anat Rec 294:1635-1645, 2011), suggesting that increased mGluR5 signaling is common to multiple autism spectrum disorders. Increased mGluR5 signaling may be associated with reduced phosphorylation of fragile X mental retardation protein (FMRP), which could result in the inactivation of this protein. In the current study, we report on reduced expression of phosphorylated FMRP in cerebellar vermis of adults and children with autism and in FC of adults with autism.
منابع مشابه
Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study
BACKGROUND Fragile × syndrome is caused by loss of function of the fragile × mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. METHODS In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and mat...
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BACKGROUND Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. METHODS In the current study we...
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Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that ...
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The fragile X mental retardation protein (FMRP) is an mRNA-binding regulator of protein translation that associates with 4-6% of brain transcripts and is central to neurodevelopment. Autism risk genes' transcripts are overrepresented among FMRP-binding mRNAs, and FMRP loss-of-function mutations are responsible for fragile X syndrome, the most common cause of monogenetic autism. It is thought th...
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