Nerve growth factor-dependent regulation of NADE-induced apoptosis

The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor (TNFR) superfamily, and can mediate both cell survival and cell death in response to nerve growth factor (NGF). Based on the structural and functional differences between p75NTR and the related receptors Fas or TNFR, it has been suggested that these receptors have distinct signaling functions. NADE (p75NTR-associated cell death executor) is a p75NTR-associated protein that mediates apoptosis in response to NGF by interacting with the cell death domain of p75NTR. NADE has at least four isoforms, designated as NADE2, NADE3, NADE4/Bex1, and NADE5/Bex2. NADE plays a role in NGF-induced apoptosis in oligodendrocytes and in zinc-induced neuronal death. In this review, we focus on the proapoptotic actions of NADE that regulate p75NTR signaling in response to NGF.