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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. [ABSTRACT FROM AUTHOR]

Amyloid precursor protein (APP) is a key molecule in the pathogenesis of Alzheimer’s disease (AD) as the pathogenic amyloid-β peptide is derived from it. Two closely related APP family proteins (APPs) have also been identified in mammals. Current knowledge, including genetic analyses of gain- and loss-of-function mutants, highlights the importance of APPs in various physiological functions. Notably, APPs consist of multiple extracellular and intracellular protein-binding regions/domains. Protein–protein interactions are crucial for many cellular processes. In past decades, many APPs interactors have been identified which assist the revelation of the putative roles of APPs. Importantly, some of these interactors have been shown to influence several APPs-mediated neuronal processes which are found defective in AD and other neurodegenerative disorders. Studying APPs–interactor complexes would not only advance our understanding of the physiological roles of APPs but also provide further insights into the association of these processes to neurodegeneration, which may lead to the development of novel therapies. In this mini-review, we summarize the roles of APPs–interactor complexes in neurodevelopmental processes including neurogenesis, neurite outgrowth, axonal guidance and synaptogenesis. [ABSTRACT FROM AUTHOR]