The AICD interactome: implications in neurodevelopment and neurodegeneration

The pathophysiological mechanism involving the proteolytic processing of amyloid precursor protein (APP) and the generation of amyloid plaques is of significant interest in research on Alzheimer's disease (AD). The increasing significance of the downstream AD-related pathophysiological mechanisms has sparked research interest in other products of the APP processing cascades, including the APP intracellular domain (AICD). The potential importance of AICD in various cellular processes in the central nervous system has been established through the identification of its interactors. The interaction between AICD and its physiological binding partners is implicated in cellular events including regulation of transcriptional activity, cytoskeletal dynamics, neuronal growth, APP processing and cellular apoptosis. On the contrary, AICD is also implicated in neurodegeneration, which is a potential outcome of the functional fluctuation of AICD-mediated neuronal processes within the neuronal network. In this review, we summarize the neuronal functions and pathological manifestations of the dynamic AICD interaction network.