tailieunhanh - Báo cáo khoa học: b-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins

The amyloid precursor family of proteins are of considerable interest, both because of their role in Alzheimer’s disease pathogenesis and because of their normal physiological functions. In mammals, the amyloid precursor protein (APP) has two homologs, amyloid precursor-like protein (APLP) 1 and APLP2. | b-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins Carlo Sala Frigerio1 Julia V. Fadeeva2 Aedín M. Minogue1 Martin Citron3 Fred Van Leuven4 Matthias Staufenbiel5 Paolo Paganetti5 Dennis J. Selkoe2 and Dominic M. Walsh1 1 Laboratory for Neurodegenerative Research The Conway Institute for Biomolecular and BiomedicalResearch University College Dublin Republic of Ireland 2 Department of Neurology Harvard MedicalSchooland Center for Neurologic Diseases Brigham and Women s Hospital Boston MA USA 3 Amgen Inc. Thousand Oaks CA USA 4 Department of Human Genetics Katholieke Universiteit Leuven Belgium 5 Nervous System Research Novartis Institutes for BiomedicalResearch Basel Switzerland Keywords Alzheimer s disease amyloid precursor protein APP amyloid precursor-like protein 1 APLP1 amyloid precursor-like protein 2 APLP2 b-site amyloid precursor protein-cleaving enzyme BACE1 Correspondence Dominic M. Walsh Laboratory for Neurodegenerative Research The Conway Institute for Biomolecular and Biomedical Research University College Dublin Belfield Dublin 4 Republic of Ireland Fax 353 1 716 6890 Tel 353 1 7166751 E-mail Present address Eli Lilly and Company Indianapolis IN 46285 USA Received 31 October 2009 revised 6 January 2010 accepted 12 January 2010 doi The amyloid precursor family of proteins are of considerable interest both because of their role in Alzheimer s disease pathogenesis and because of their normal physiological functions. In mammals the amyloid precursor protein APP has two homologs amyloid precursor-like protein APLP 1 and APLP2. All three proteins undergo ectodomain shedding and regulated intramembrane proteolysis and important functions have been attributed to the full-length proteins shed ectodomains C-terminal fragments and intracellular domains ICDs . One of the proteases that is known to cleave APP and that is essential