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• W2153669928 abstract "BACE1 is a key enzyme in the generation of the Abeta peptide that plays a central role in the pathogenesis of Alzheimer's disease. While BACE1 is an attractive therapeutic target, its normal physiological function remains largely unknown. Examination of BACE1-/- mice can provide insight into this function and also help anticipate consequences of BACE1 inhibition. Here we report a seizure-susceptibility phenotype that we have identified and characterized in BACE1-/- mice.We find that electroencephalographic recordings reveal epileptiform abnormalities in some BACE1-/- mice, occasionally including generalized tonic-clonic and absence seizures. In addition, we find that kainic acid injection induces seizures of greater severity in BACE1-/- mice relative to BACE1+/+ littermates, and causes excitotoxic cell death in a subset of BACE1-/- mice. This hyperexcitability phenotype is variable and appears to be manifest in approximately 30% of BACE1-/- mice. Finally, examination of the expression and localization of the voltage-gated sodium channel alpha-subunit Nav1.2 reveals no correlation with BACE1 genotype or any measure of seizure susceptibility.Our data indicate that BACE1 deficiency predisposes mice to spontaneous and pharmacologically-induced seizure activity. This finding has implications for the development of safe therapeutic strategies for reducing Abeta levels in Alzheimer's disease. Further, we demonstrate that altered sodium channel expression and axonal localization are insufficient to account for the observed effect, warranting investigation of alternative mechanisms." @default.
• W2153669928 created "2016-06-24" @default.
• W2153669928 creator A5028697711 @default.
• W2153669928 creator A5058218282 @default.
• W2153669928 creator A5074699244 @default.
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• W2153669928 date "2010-08-23" @default.
• W2153669928 modified "2023-10-07" @default.
• W2153669928 title "BACE1-/- mice exhibit seizure activity that does not correlate with sodium channel level or axonal localization" @default.
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• W2153669928 doi "https://doi.org/10.1186/1750-1326-5-31" @default.
• W2153669928 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2933677" @default.
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• W2153669928 hasPublicationYear "2010" @default.
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