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- W1965351504 abstract "A better understanding of the cellular and molecular pathomechanisms of Alzheimer's disease (AD) is a prerequisite for the development of efficient treatments. We have used a novel assay system based on virus-transduced organotypic hippocampal slice cultures that mimics important aspects of tau-driven AD pathology in a short time frame. Human tau P301L, when expressed in pyramidal neurons of hippocampal slice cultures, was increasingly phosphorylated at several disease-relevant epitopes, leading to progressive neuronal dystrophy and formation of RIPA-insoluble tau. AD-like tau hyperphosphorylation was reduced by the tau kinase inhibitors lithium and SRN-003-556, but RIPA-insoluble tau remained unaffected after treatment with any of these substances. Only SRN-003-556 was able to protect hippocampal neurons from synaptic damage that was presumably caused by a toxic soluble tau fraction. These data provide first mechanistic insights towards the functional benefits of SRN-003-556 that have been observed in vivo." @default.
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- W1965351504 date "2008-03-01" @default.
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- W1965351504 title "Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation" @default.
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- W1965351504 doi "https://doi.org/10.1016/j.mcn.2007.12.004" @default.
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