Secretases Related to Amyloid Precursor Protein Processing [PDF]
Membranes, 2021 Alzheimer’s disease (AD) is a common neurodegenerative disease whose prevalence increases with age. An increasing number of findings suggest that abnormalities in the metabolism of amyloid precursor protein (APP), a single transmembrane aspartic protein that is cleaved by β- and γ-secretases to produce β-amyloid protein (Aβ), are a major pathological ...
Xiaoling Liu, Yan Liu, Shangrong Ji
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Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation [PDF]
Nature Communications, 2012 In sporadic age-related forms of Alzheimer's disease (AD), it is unclear why amyloid-β (Aβ) peptides accumulate. Here we show that soluble amyloid precursor protein-α (sAPP-α) decreases Aβ generation by directly associating with β-site APP-converting enzyme (BACE)1, thereby modulating APP processing.
Demian, Obregon +10 more
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Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease [PDF]
Alzheimer's Research & Therapy, 2010 Abstract Introduction Inhibition of gamma-secretase presents a direct target for lowering Aβ production in the brain as a therapy for Alzheimer's disease (AD). However, gamma-secretase is known to process multiple substrates in addition to amyloid precursor protein (APP), most notably Notch, which has ...
Basi, Guriqbal S +51 more
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Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol [PDF]
Cell & Bioscience, 2023 Amyloid β is considered a key player in the development and progression of Alzheimer’s disease (AD). Many studies investigating the effect of statins on lowering cholesterol suggest that there may be a link between cholesterol levels and AD pathology ...
Vladimir Rudajev, Jiri Novotny
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γ‐Secretase modulators show selectivity for γ‐secretase–mediated amyloid precursor protein intramembrane processing [PDF]
Journal of Cellular and Molecular Medicine, 2021 AbstractThe aggregation of β‐amyloid peptide 42 results in the formation of toxic oligomers and plaques, which plays a pivotal role in Alzheimer's disease pathogenesis. Aβ42 is one of several Aβ peptides, all of Aβ30 to Aβ43 that are produced as a result of γ‐secretase–mediated regulated intramembrane proteolysis of the amyloid precursor protein.
Tobias A. Weber +15 more
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Cholesterol Modulates α-Secretase Cleavage of Amyloid Precursor Protein [PDF]
Journal of Biological Chemistry, 1996 Amyloid precursor protein (APP) and cholesterol metabolism are genetically linked to Alzheimer's disease, the latter through apolipoprotein E, a lipid and cholesterol transport protein. We have examined the hypothesis that the processing of APP is disrupted by elevated cholesterol, which is known to modulate the activity of several transmembrane ...
S, Bodovitz, W L, Klein
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β-Amyloid Precursor Protein Mutants Respond to γ-Secretase Modulators [PDF]
Journal of Biological Chemistry, 2010 Pathogenic generation of the 42-amino acid variant of the amyloid beta-peptide (Abeta) by beta- and gamma-secretase cleavage of the beta-amyloid precursor protein (APP) is believed to be causative for Alzheimer disease (AD). Lowering of Abeta(42) production by gamma-secretase modulators (GSMs) is a hopeful approach toward AD treatment. The mechanism of
Page, Richard M +5 more
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GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein [PDF]
Science Translational Medicine, 2021 GDE2 controls surface amounts of the metalloprotease inhibitor RECK to promote ADAM10 α-secretase activity and prevent Aβ production and synapse loss.
Nakamura, Mai +7 more
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A reporter for amyloid precursor protein -secretase activity in Drosophila [PDF]
Human Molecular Genetics, 2003 A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as beta-amyloid (Abeta) that is derived from the amyloid precursor protein (APP). A proteolytic activity called gamma-secretase cleaves APP in the transmembrane domain and is required for Abeta generation. Aberrant gamma-
Guo, Ming +4 more
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Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer's disease. [PDF]
PLoS ONE, 2011 BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life.
Naoki Yahata +13 more
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