Notch Signaling and CNS

Notch signaling is initiated and activated by direct cell-cell interactions that facilitate binding between the four Notch receptor isoforms (Notch1-4) to the transmembrane Notch ligands Delta (DLL1 and DLL4) or Jagged-type (Jagged-1 and Jagged-2). These ligands initiate the proteolytic cleavage of Notch receptors by the metalloproteases TACE (ADAM17) or ADAM10, which then are further processed by a γ-secretase-presenilin complex, which releases the cytosolic portion of Notch receptors.This intracellular domain of Notch (NICD)translocates into the cell nucleus, induces transcriptional processes and the expression of target genes and consequently proteins (e.g. HES).

Notch signaling inhibits neuronal differentiation in the developing central nervous system and is implicated in the maintenance of neuronal stem cells (NSCs), regulating differentiation, self-renewal, neurogenesis and gliogenesis. Recent findings suggest that Notch signaling pathway could be implicated in pathogenesis of neurodegenerative disorders.