Results 11 to 20 of about 14,023 (271)
Interactions between APP secretases and inflammatory mediators [PDF]
Journal of Neuroinflammation, 2008 There is now a large body of evidence linking inflammation to Alzheimer's disease (AD). This association manifests itself neuropathologically in the presence of activated microglia and astrocytes around neuritic plaques and increased levels of ...
Gentleman Steve M +2 more
doaj +6 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
A thermodynamic investigation of amyloid precursor protein processing by human γ-secretase [PDF]
Communications Biology, 2022 AbstractHuman γ-secretase cleaves the transmembrane domains (TMDs) of amyloid precursor protein (APP) into pathologically relevant amyloid-β peptides (Aβs). The detailed mechanisms of the unique endoproteolytic cleavage by the presenilin 1 domain (PS1) of γ-secretase are still poorly understood.
Xiaoli Lu, Jing Huang
openalex +4 more sources
Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. [PDF]
Brain Res, 2014 Amyloid-β (Aβ) is produced through the enzymatic cleavage of amyloid precursor protein (APP) by β (Bace1) and γ-secretases. The accumulation and aggregation of Aβ as amyloid plaques is the hallmark pathology of Alzheimer׳s disease and has been found in other neurological disorders, such as traumatic brain injury and multiple sclerosis.
Pajoohesh-Ganji A +6 more
europepmc +4 more sources
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
openaire +2 more sources
Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. [PDF]
Nat Med, 2009 Amyloid-beta (Abeta) peptides, found in Alzheimer's disease brain, accumulate rapidly after traumatic brain injury (TBI) in both humans and animals. Here we show that blocking either beta- or gamma-secretase, enzymes required for production of Abeta from amyloid precursor protein (APP), can ameliorate motor and cognitive deficits and reduce cell loss ...
Loane DJ +7 more
europepmc +4 more sources
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
openaire +2 more sources
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
openaire +4 more sources