Notch signaling pathway (Notch 1-HES axis) (Notch 1-HES pathway)

The Notch signaling pathway (Notch 1-HES axis) is a highly conserved cell-cell communication pathway essential for proper embryonic development, cell fate specification, proliferation, and tissue homeostasis. Notch 1, a single-pass transmembrane receptor, upon ligation, undergoes proteolytic cleavage releasing its intracellular domain (NICD), which translocates to the nucleus and complexes with transcription factors to regulate genes such as HES1, a basic helix-loop-helix (bHLH) transcriptional repressor. Dysregulation of this pathway is implicated in diverse diseases including cancer, cardiovascular disorders, and immune dysfunction. Inhibition of the pathway, particularly with γ-secretase inhibitors, is under clinical investigation, but toxicity due to the pathway’s roles in normal tissue homeostasis remains a major therapeutic challenge.

Other names

Notch 1 signaling pathwayNotch 1-HES1 pathwayNotch 1 intracellular domain-HES axis

Inhibit γ-secretase to block Notch receptor cleavage and nuclear translocation of Notch intracellular domain Antibodies block receptor or ligand to prevent activation of receptor-mediated signaling Down-regulate Notch target gene expression (e.g., HES1 repression)