The X11 proteins, Abeta production and Alzheimer's disease.
Cerebral deposition of amyloid-beta peptide (Abeta) within neuritic plaques is a hallmark pathology of Alzheimer's disease. It is now generally believed that the development of this pathology is central to the pathogenesis of Alzheimer's disease. As such, inhibiting Abeta deposition or removing Abeta deposits once they are formed represent therapeutic targets for Alzheimer's disease. Abeta is derived from a precursor, the amyloid precursor protein (APP), and APP binds to the X11 family of adaptor proteins. Studies from several laboratories have now shown that X11alpha and X11beta (the two neuronal X11s) inhibit APP processing and Abeta production. Exactly how this is achieved is not yet known but recent studies in which other X11 binding partners have been identified are beginning to reveal potential mechanisms.
MRC Centre for Neurodegeneration Research, Departments of Neuroscience and Section of Old Age Psychiatry PO37, Institute of Psychiatry, King's College, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. chris.miller@iop.kcl.ac.uk
Christopher C J
CC
Miller
Declan M
DM
McLoughlin
Kwok-Fai
KF
Lau
Maria E
ME
Tennant
Boris
B
Rogelj
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D025941:Protein Interaction Mapping; D015398:Signal Transduction / Q000502:physiology
C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C513072:Apba1 protein, mouse; C491635:Apba2 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D003300:Copper; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse