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 ?-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 ?-amyloid precursor protein alpha (sAPP?), sAPP?, and amyloid ? (A?). Binding of A? to p75^NTR induces neuronal death. In contrast, sAPP? 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.