title: The physiology of the β-amyloid precursor protein intracellular domain AICD.
abstract: The amyloid-β precursor protein (βAPP) undergoes several cleavages by enzymatic activities called secretases. Numerous studies aimed at studying the biogenesis and catabolic fate of Aβ peptides, the proteinaceous component of the senile plaques that accumulate in Alzheimer's disease-affected brains. Relatively recently, another secretase-mediated β-APP-derived catabolite called APP IntraCellular Domain (AICD) entered the game. Whether AICD corresponded to a biologically inert by-pass product of βAPP 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 Aβ degradation.
authors: Université de Nice Sophia-Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire UMR6097 CNRS, Equipe labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France.
authors: Raphaëlle
authors: R
authors: Pardossi-Piquard
authors: Université de Nice Sophia-Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire UMR6097 CNRS, Equipe labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France.
authors: Frédéric
authors: F
authors: Checler
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D003593:Cytoplasm / Q000737:chemistry* / Q000502:physiology; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry* / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D014157:Transcription Factors; D053829:Amyloid Precursor Protein Secretases