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.

Transcriptional and Post-transcriptional Regulation of beta-secretase

TAMAGNO, Elena;GUGLIELMOTTO, Michela;MONTELEONE, DEBORA;VERCELLI, Alessandro;
2012

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.
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E. Tamagno; M. Guglielmotto; D. Monteleone; A. Vercelli; M. Tabaton
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/133127
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