Intracellular biology of Alzheimer's disease amyloid beta peptide.
Strong evidence links excess production of a small peptide and the pathogenesis of Alzheimer's disease (AD). Originally this peptide, beta-amyloid 42 (Abeta42), was assumed to be released by a pathogenic event; it is now well established that Abeta42 is released from cells during normal cellular metabolism of the Alzheimer amyloid precursor protein. Recently, in a series of surprising reports it was discovered that Abeta42 is produced intracellularly, and what might have been regarded first as a strange abnormality of a few selected cell lines has now been recognized as an important cellular pathway for Abeta production. Moreover, the differences between secretory and intracellular Abeta production might hold the clues for brain specificity and cellular mechanisms of AD pathogenesis.
Hartmann
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Center for Molecular Biology (ZMBH), University of Heidelberg, Germany. tobias.hartmann@mail.zmbh.uni-heidelberg.de
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D058225:Plaque, Amyloid / Q000378:metabolism*; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human