Glycogen synthase kinase 3 beta (GSK-3β) (GSK-3β)

Glycogen synthase kinase 3 beta (GSK-3β) is a proline-directed serine/threonine protein kinase encoded by the GSK3B gene in humans[2][1]. It is a multifunctional enzyme involved in diverse processes, including energy metabolism, neuronal development, apoptosis, and regulation of gene transcription[2][3][4][6]. GSK-3β is a central negative regulator of the canonical Wnt/β-catenin signaling pathway, where it phosphorylates β-catenin in a multiprotein destruction complex, targeting β-catenin for degradation and thus inhibiting its transcriptional activity[1][3][4][5][6]. Dysregulation or hyperactivation of GSK-3β is implicated in the pathogenesis of several diseases, including cancer, neurodegenerative disorders (such as Alzheimer’s disease), diabetes, mood disorders, and chronic inflammation[1][2][3]. GSK-3β and its pathway are considered significant therapeutic targets, with multiple small molecule inhibitors under preclinical and clinical development for diseases ranging from cancer to neurodegeneration and mental health disorders[1][2].

Other names

GSK3BGlycogen synthase kinase-3 beta

Inhibition of GSK-3β kinase activity leading to increased β-catenin stability and activation of Wnt/β-catenin signaling - Downregulation of β-catenin phosphorylation and ubiquitin-mediated degradation - Modulation of downstream gene expression profiles involved in cell fate, proliferation, or survival