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Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Abeta) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome.(More)
Fragile X syndrome (FXS) is a common inherited cause of mental retardation resulting from the absence of the fragile X mental retardation protein (FMRP). FMRP is thought to regulate the translation of target mRNAs, including its own transcript. Here we show that the levels of FMRP are rapidly up-regulated in primary cortical neurons in response to the(More)
Fragile X syndrome is a common inherited cause of mental retardation that results from the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein thought to regulate translation of bound mRNAs, including its own. Previous studies in our laboratory have shown that FMRP expression increases in the barrel cortex of the rat after(More)
Extensive β-amyloid (Aβ) deposits in brain parenchyma in the form of senile plaques and in blood vessels in the form of amyloid angiopathy are pathological hallmarks of Alzheimer's disease (AD). The mechanisms underlying Aβ deposition remain unclear. Major efforts have focused on Aβ production, but there is little to suggest that increased production of Aβ(More)
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid β-protein precursor (AβPP) mRNA. Cleavage of AβPP(More)
Alzheimer's disease and Fragile X syndrome both display synaptic phenotypes, and based on recent studies, likely share dendritic over expression of amyloid precursor protein (APP) and beta-amyloid (Abeta). In order to create a mouse model to specifically study the effects of APP and Abeta at synapses, we crossed Tg2576, which over-express human APP with the(More)
The cerebral accumulation of beta-amyloid (Abeta) is a consistent feature of and likely contributor to the development of Alzheimer's disease. In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism also plays an important role in Abeta accumulation. We have previously shown that neprilysin (NEP), the major(More)
Amyloid-beta protein precursor (AbetaPP) is overexpressed in Alzheimer's disease (AD), Down syndrome (DS), autism, and fragile X syndrome. Seizures are a common phenotype in all of these neurological disorders, yet the underlying molecular mechanism(s) of seizure induction and propagation remain largely unknown. We demonstrate that AD (Tg2576) and DS(More)
Seizures are a common phenotype in many neurological disorders including Alzheimer's disease, Down syndrome, and fragile X syndrome. Mouse models of these disorders overexpress amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) and are highly susceptible to audiogenic-induced seizures (AGS). We observed decreased AGS in these mice fed a casein-based,(More)