Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer's patient-derived cortical neurons.

ABSTRACT: Hyperphosphorylation of Tau and the ensuing microtubule destabilization are linked to synaptic dysfunction in Alzheimer's disease (AD). We find a marked increase of phosphorylated Tau (pTau) in cortical neurons differentiated from induced pluripotent stem cells (iPSCs) of AD patients. It is accompanied by significantly elevated expression of Serum and Glucocorticoid-regulated Kinase-1 (SGK1), which is induced by cellular stress, and Histone Deacetylase 6 (HDAC6), which deacetylates tubulin to destabilize microtubules. Indeed, acetylated tubulin and microtubule stability are significantly lower in AD-derived cortical neurons. SGK1 inhibitors or shRNA decrease Tau phosphorylation and HDAC6 levels while increasing acetylated tubulin in AD neurons. Overexpression of SGK1 in normal neurons does

SUBMITTER: Saleem K 

PROVIDER: S-EPMC12700806 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature