Novel screening cascade identifies MKK4 as key kinase regulating Tau phosphorylation at Ser422 |
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Authors: | Fiona Grueninger Bernd Bohrmann Klaus Christensen Martin Graf Doris Roth Christian Czech |
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Institution: | CNS Discovery and Translation Pharma Research and Exploratory Development, F. Hoffmann-La Roche AG, Basel, Switzerland. fiona.grueninger@roche.com |
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Abstract: | Phosphorylation of Tau at serine 422 promotes Tau aggregation. The kinase that is responsible for this key phosphorylation event has so far not been identified but could be a potential drug target for Alzheimer's disease. We describe here an assay strategy to identify this kinase. Using a combination of screening a library of 65'000 kinase inhibitors and in vitro inhibitor target profiling of the screening hits using the Ambit kinase platform, MKK4 was identified as playing a key role in Tau-S422 phosphorylation in human neuroblastoma cells. |
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