The physiology of the beta-amyloid precursor protein intracellular domain AICD

The amyloid-beta precursor protein (beta APP) undergoes several cleavages by enzymatic activities called secretases. Numerous studies aimed at studying the biogenesis and catabolic fate of A beta peptides, the proteinaceous component of the senile plaques that accumulate in Alzheimers disease-affected brains. Relatively recently, another secretase-mediated beta-APP-derived catabolite called APP IntraCellular Domain (AICD) entered the game. Whether AICD corresponded to a biologically inert by-pass product of beta APP processing or whether it could harbor its own function remained questionable. In this study, we review the mechanisms by which AICD is generated and how its production is regulated. Furthermore, we discuss the degradation mechanism underlying its rapid catabolic fate. Finally, we review putative AICD-related functions and more particularly, the numerous studies indicating that AICD could translocate to the nucleus and control at a transcriptional level, the expression of a series of proteins involved in various functions including the control of cell death and A beta degradation.