Amyloid-beta precursor protein processing in neurodegeneration.
The amyloid-beta precursor protein is proteolytically cleaved by secretases, resulting in a series of fragments, including the amyloid-beta peptide of Alzheimer's disease. The amyloid precursor protein, when membrane anchored, could operate as a receptor. After cleavage, the soluble ectodomain exerts a trophic function in the subventricular zone. The amyloid-beta peptide itself has a depressant role in synaptic transmission, with both physiological and pathological implications. During the past two years, much time has been invested in determining the molecular pathways that regulate the processing and the signal transduction of the amyloid precursor protein. However, the absence of consistent and informative phenotypes in different loss of function animal models make elucidating the molecular actions of the amyloid-beta precursor protein an ongoing challenge.
Laboratory for Neuronal Cell Biology and Gene Transfer, K.U. Leuven and VIB, Department of Human Genetics, Herestraat 49, 3000 Leuven, Belgium. bart.destrooper@med.kuleuven.ac.be
Valérie
V
Wilquet
Bart
B
De Strooper
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human