The Receptor for Advanced Glycation End-products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors which interacts with a wide range of ligands, such as High-Mobility Group Box-1 (HMGB-1), S100B, advanced glycation end-products (AGEs). Here we provided evidence for the restricted expression of RAGE in the undifferentiated neural stem/progenitor cells of mouse adult SubVentricular Zone (SVZ) neurogenic region and adult SVZ-derived neurospheres. Additionally, RAGE ligands stimulated both proliferation and neuronal differentiation of SVZ-derived neural progenitor cells (NPC) in vitro. NF-kappaB nuclear translocation occurred upon RAGE activation in SVZ-derived neurospheres and its blockade (by SN-50) or its absence (in p50(-/-) derived NPC) resulted in the inhibition of the ligand-mediated effects on neuronal differentiation. These novel findings delineate an interesting scenario where the RAGE-NF-kappaB axis may contribute to regulate adult neural stem/progenitor cell function in physiological and possibly pathological conditions where this axis is upregulated.