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

Authors

  • Raphaëlle Pardossi-Piquard,

    1. Université de Nice Sophia-Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire UMR6097 CNRS, Equipe labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France
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  • Frédéric Checler

    1. Université de Nice Sophia-Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire UMR6097 CNRS, Equipe labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France
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Address correspondence and reprint requests to F. Checler, Université de Nice Sophia-Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire UMR6097 CNRS, Equipe labellisée Fondation pour la Recherche Médicale, 660 route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France. E-mail: checler@ipmc.cnrs.fr

Abstract

J. Neurochem. (2012) 120 (Suppl. 1), 109–124.

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.

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