Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer's disease.

ABSTRACT: Dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A) is known to phosphorylate the microtubule-associated tau protein. Overexpression is correlated with tau hyperphosphorylation and neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD). This study assessed the potential of SM07883, an oral DYRK1A inhibitor, to inhibit tau hyperphosphorylation, aggregation, NFT formation, and associated phenotypes in mouse models. Exploratory neuroinflammatory effects were also studied. SM07883 specificity was tested in a kinase panel screen and showed potent inhibition of DYRK1A (IC₅₀  = 1.6 nM) and GSK-3β (IC₅₀  = 10.8 nM) kinase activity. Tau phosphorylation measured in cell-based assays showed a reduction in phosphorylation of multiple tau epitopes, e

SUBMITTER: Melchior B 

PROVIDER: S-EPMC6718548 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature