biostudies-literatureKim BMNIA NIH HHSNIMH NIH HHSe1237https://www.ebi.ac.uk/biostudies/studies/S-EPMC4047864biostudies-literatureUnknown5The presence of tangles composed of phosphorylated tau is one of the neuropathological hallmarks of Alzheimer's disease (AD). Tau, a microtubule (MT)-associated protein, accumulates in AD potentially as a result of posttranslational modifications, such as hyperphosphorylation and conformational changes. However, it has not been fully understood how tau accumulation and phosphorylation are deregulated. In the present study, we identified a novel role of death-associated protein kinase 1 (DAPK1) in the regulation of the tau protein. We found that hippocampal DAPK1 expression is markedly increased in the brains of AD patients compared with age-matched normal subjects. DAPK1 overexpression increased tau protein stability and phosphorylation at multiple AD-related sites. In contrast, inhibitionCell death & diseaseDeath-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function.PMC4047864R24MH068855P50 AG005134T32AG023480R00 AG033104T32 AG023480R00AG033104R24 MH068855P50AG05134Lee SZhou XZHong YLee THKim BMChen CHKimchi AYou MHfalseDeath-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function.The presence of tangles composed of phosphorylated tau is one of the neuropathological hallmarks of Alzheimer's disease (AD). Tau, a microtubule (MT)-associated protein, accumulates in AD potentially as a result of posttranslational modifications, such as hyperphosphorylation and conformational changes. However, it has not been fully understood how tau accumulation and phosphorylation are deregulated. In the present study, we identified a novel role of death-associated protein kinase 1 (DAPK1) in the regulation of the tau protein. We found that hippocampal DAPK1 expression is markedly increased in the brains of AD patients compared with age-matched normal subjects. DAPK1 overexpression increased tau protein stability and phosphorylation at multiple AD-related sites. In contrast, inhibition2014-01-01T00:00:00Z2014 May2025-04-18T23:14:55.826Z2019-03-27T01:29:36ZS-EPMC40478642485341510.1038/cddis.2014.216