Overwhelming evidence indicates that the Aβ (amyloid β-peptide) plays a critical role in the pathogenesis of Alzheimer's disease. Aβ is derived from the APP (amyloid precursor protein) by the action of two aspartyl proteases (β- and γ-secretases) that are leading candidates for therapeutic intervention. APP is a member of a multigene family that includes APLP1 (amyloid precursor-like protein 1) and APLP2. Both APLPs are processed in a manner analogous to APP, with all three proteins subject to ectodomain shedding and subsequent cleavage by γ-secretase. Careful study of the APP family of proteins has already revealed important insights about APP. Here, we will review how knowledge of the similarities and differences between APP and the APLPs may prove useful for the development of novel disease-modifying therapeutics.
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April 2007
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Conference Article|
March 20 2007
The APP family of proteins: similarities and differences
D.M. Walsh;
D.M. Walsh
1
*Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
†Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, U.S.A.
1To whom correspondence should be addressed (email dominic.walsh@ucd.ie).
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A.M. Minogue;
A.M. Minogue
*Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
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C. Sala Frigerio;
C. Sala Frigerio
*Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
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J.V. Fadeeva;
J.V. Fadeeva
†Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, U.S.A.
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W. Wasco;
W. Wasco
‡Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, U.S.A.
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D.J. Selkoe
D.J. Selkoe
†Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, U.S.A.
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Publisher: Portland Press Ltd
Received:
October 05 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 The Biochemical Society
2007
Biochem Soc Trans (2007) 35 (2): 416–420.
Article history
Received:
October 05 2006
Citation
D.M. Walsh, A.M. Minogue, C. Sala Frigerio, J.V. Fadeeva, W. Wasco, D.J. Selkoe; The APP family of proteins: similarities and differences. Biochem Soc Trans 1 April 2007; 35 (2): 416–420. doi: https://doi.org/10.1042/BST0350416
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