title: Transcriptional and post-transcriptional regulation of β-secretase.
abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that results in loss of memory and cognitive function, eventually leading to dementia. A key neuropathological event in AD is the cerebral accumulation of senile plaques formed by aggregates of amyloid-β-peptides (Aβ). Aβ results from two sequential endoproteolytic cleavages operated on the amyloid-β precursor protein (AβPP), an integral membrane protein with a single-membrane spanning domain, a large extracellular N-terminus and a shorter, cytoplasmic C-terminus. First, β-secretase (BACE1) cleaves AβPP at the N-terminal end of the Aβ sequence to produce a secreted form of AβPP, named sAβPP, and a C-terminal membrane-bound 99-aminoacid fragment (C99). Then, γ-secretase cleaves C99 within the transmembrane domain to release the Aβ peptides of different lengths, predominantly Aβ1-40 and Aβ1-42.
authors.affiliation: Department of Neuroscience, University of Torino, Torino, Italy. elena.tamagno@unito.it
authors.forename: Elena
authors.initials: E
authors.lastname: Tamagno
authors.forename: M
authors.initials: M
authors.lastname: Guglielmotto
authors.forename: D
authors.initials: D
authors.lastname: Monteleone
authors.forename: A
authors.initials: A
authors.lastname: Vercelli
authors.forename: M
authors.initials: M
authors.lastname: Tabaton
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human