A thermodynamic investigation of amyloid precursor protein processing by human γ-secretase [PDF]
Communications Biology, 2022 Thermodynamic analysis from unbiased molecular dynamics and bias-exchange metadynamics simulations reveals possible mechanisms on how γ-secretase cleaves the transmembrane domains of amyloid precursor protein into amyloid-β peptides.
Xiaoli Lu, Jing Huang
doaj +4 more sources
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
doaj +2 more sources
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, Shang‐Rong Ji
openalex +5 more sources
The multifaceted roles of the transcription factor <i>SP1</i> in the pathogenesis of Alzheimer's disease: From molecular regulation to therapeutic targets. [PDF]
Alzheimers Dement (N Y)Abstract Alzheimer's disease (AD) is driven by interrelated pathologies, including the accumulation of amyloid β (Aβ), tau pathology, chronic neuroinflammation, and oxidative stress (OS). These pathological processes collectively lead to progressive neurodegeneration.
Lv Z, Liu X, Huang Q, Liu H, Xu Z, Xu P.
europepmc +2 more sources
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
openalex +3 more sources
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
openaire +3 more sources
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 ...
Guriqbal S. Basi +51 more
openalex +4 more sources
PLoS ONE, 2022 The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer's disease. These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ ...
Edward T Parkin +3 more
doaj +1 more source
Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase [PDF]
Journal of Cell Biology, 2003 Zoe Scholefield +5 more
openalex +3 more sources
Altered processing of amyloid precursor protein in cells undergoing apoptosis. [PDF]
PLoS ONE, 2013 Altered proteolysis of amyloid precursor protein is an important determinant of pathology development in Alzheimer's disease. Here, we describe the detection of two novel fragments of amyloid precursor protein in H4 neuroglioma cells undergoing apoptosis.
Tina Fiorelli +2 more
doaj +1 more source