The functions and signaling pathways induced by the interactions of APP–related molecules with p75NTR

Abstract

p75 neurotrophin receptor (p75 NTR ) regulates diverse functions, including survival, differentiation, growth, and apoptosis of neurons, through its association with a number of molecules. Accumulating evidence shows that β-amyloid precursor protein (APP)–related molecules, which also regulate multiple neuronal functions, interact with p75 NTR . APP is cleaved by secretases to generate several proteins including soluble β-amyloid precursor protein alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Binding of Aβ to p75 NTR induces neuronal death. In contrast, sAPPα directly interacts with p75 NTR to enhance neurite outgrowth through the activation of protein kinase A (PKA). This review focuses on the molecular mechanisms and functions occurring as a consequence of interactions of p75 NTR with APP–related molecules.