APPepsilon, the epsilon-secretase-derived N-terminal product of the beta-amyloid precursor protein, behaves as a type I protein and undergoes alpha-, beta-, and gamma-secretase cleavages

Journal of Neurochemistry
Solveig Lefranc-JullienFrédéric Checler

Abstract

beta-Amyloid peptide accumulates in the brain of patients affected by sporadic or familial forms of Alzheimer's disease. It derives from the proteolytic attacks of the beta-amyloid precursor protein (betaAPP) by beta- and gamma-secretase activities. An additional epsilon cleavage taking place a few residues C-terminal to the gamma-site has been reported, leading to the formation of an intracellular fragment referred to as APP intracellular domain C50. This epsilon cleavage received particular attention because it resembles the S3 Notch cleavage generating Notch intracellular domain. Indeed, APP intracellular domain, like its Notch counterpart, appears to mediate important physiological functions. gamma and epsilon cleavages on betaAPP appear spatio-temporally linked but pharmacologically distinct and discriminable by mutagenesis approaches. As these cleavages could be seen as either deleterious (gamma-site) or beneficial (epsilon-site), it appears of most interest to set up models aimed at studying these activities separately, particularly to design specific and bioavailable inhibitors. On the other hand, it is important to respect the topology of the substrates in order to examine physiologically relevant cleavages. Here we de...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S Sisodia
Nov 1, 1996·Journal of Neuroscience Research·P A PaganettiM Staufenbiel
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·D LevitanI Greenwald
Jan 15, 1997·The Biochemical Journal·N M HooperA J Turner
Jun 1, 1997·British Journal of Pharmacology·N ChevallierF Checler
Jan 23, 1998·Journal of Medicinal Chemistry·M S WolfeD J Selkoe
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S LammichF Fahrenholz
May 17, 2000·Proceedings of the National Academy of Sciences of the United States of America·L KulicC Haass
Aug 23, 2000·The Journal of Biological Chemistry·B VincentF Checler
Jan 9, 2001·Journal of Neurochemistry·H F DoveyJ E Audia
Apr 23, 2002·Nature Reviews. Neuroscience·Sangram S Sisodia, Peter H St George-Hyslop
May 4, 2002·Nature Cell Biology·William P EslerMichael S Wolfe
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tobias MoehlmannHarald Steiner
Jan 7, 2003·Genes & Development·Darren F Seals, Sara A Courtneidge
Jan 24, 2003·Expert Opinion on Therapeutic Targets·Martin Citron
Mar 20, 2003·The Journal of Biological Chemistry·Anna Y KornilovaMichael S Wolfe
Nov 5, 2003·Journal of Neuroscience Research·Tobias M J AllinsonNigel M Hooper
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yue Qi-TakaharaYasuo Ihara

❮ Previous
Next ❯

Citations

Sep 21, 2011·Journal of Molecular Neuroscience : MN·Natalia N NalivaevaAnthony J Turner
Aug 28, 2009·The Journal of Biological Chemistry·Raphaëlle Pardossi-PiquardPaul E Fraser
Jun 29, 2007·Neuro-degenerative Diseases·Daniele ZacchettiJacopo Meldolesi
Nov 30, 2013·Pharmacology & Therapeutics·Frédéric Checler, Cristine Alves da Costa
May 21, 2013·FEBS Letters·Natalia N Nalivaeva, Anthony J Turner
Apr 15, 2008·Biochemical and Biophysical Research Communications·Virginia DolciniFrédéric Checler
Mar 19, 2009·The FEBS Journal·Clare E Hunt, Anthony J Turner
Jul 31, 2013·European Journal of Pharmacology·Stefano MusardoElena Marcello
Feb 12, 2008·The Journal of Biological Chemistry·Virginie Buggia-PrevotFrédéric Checler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.