PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 27155148-5 2016 Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3beta cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of beta-amyloid (Abeta), beta-secretase (BACE), and reactive oxygen species (ROS). Cholesterol 143-154 beta-secretase 1 Homo sapiens 208-222 32555166-6 2020 We showed that NaB decreased the expression levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and Abeta accumulation induced by high cholesterol in SK-N-MC cells. Cholesterol 155-166 beta-secretase 1 Homo sapiens 54-107 32555166-6 2020 We showed that NaB decreased the expression levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and Abeta accumulation induced by high cholesterol in SK-N-MC cells. Cholesterol 155-166 beta-secretase 1 Homo sapiens 109-114 28059793-6 2017 High levels of cholesterol were found to enhance the maturation of AbetaPP and altered the expression and subcellular localization of ADAM10, BACE1, and PS1 thereby promoting Abeta generation, whereas high isoprenoids increased both maturation as well as amyloidogenic-cleavage of AbetaPP, which was evident through beta-CTF production. Cholesterol 15-26 beta-secretase 1 Homo sapiens 142-147 33296223-6 2021 Altering cholesterol metabolism using statins decreased generation of sAPPbeta and increased levels of full-length APP (flAPP), indicative of reduced processing of APP by BACE1. Cholesterol 9-20 beta-secretase 1 Homo sapiens 171-176 33296223-8 2021 Additionally, statin induced changes in APP dimerization and APP-BACE1 are dependent on cholesterol binding to APP. Cholesterol 88-99 beta-secretase 1 Homo sapiens 65-70 33296223-9 2021 Our data indicate that statins reduce Abeta production by decreasing BACE1 interaction with flAPP and suggest that this process may be regulated through competition between APP dimerization and APP cholesterol binding. Cholesterol 198-209 beta-secretase 1 Homo sapiens 69-74 27155148-5 2016 Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3beta cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of beta-amyloid (Abeta), beta-secretase (BACE), and reactive oxygen species (ROS). Cholesterol 143-154 beta-secretase 1 Homo sapiens 224-228 23805206-3 2013 Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (beta-secretase) transcription and down-regulation of ADAM10 (alpha-secretase) transcription which should increase release of Abeta from APP. Cholesterol 105-116 beta-secretase 1 Homo sapiens 148-153 26096015-6 2015 We found that cholesterol exposure induced astrocyte activation, increased APP content, and enhanced the interaction of APP with BACE-1. Cholesterol 14-25 beta-secretase 1 Homo sapiens 129-135 23951005-3 2013 In the present study, we show that the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) increases BACE1 and Abeta levels in human neuroblastoma SH-SY5Y cells. Cholesterol 39-50 beta-secretase 1 Homo sapiens 110-115 23443094-0 2012 Cholesterol-dependent energy transfer between fluorescent proteins-insights into protein proximity of APP and BACE1 in different membranes in Niemann-Pick type C disease cells. Cholesterol 0-11 beta-secretase 1 Homo sapiens 110-115 22551668-0 2012 Cholesterol-depletion corrects APP and BACE1 misstrafficking in NPC1-deficient cells. Cholesterol 0-11 beta-secretase 1 Homo sapiens 39-44 22551668-2 2012 We previously reported that cholesterol accumulation in NPC-cells leads to cholesterol-dependent increased APP processing by beta-secretase (BACE1) and decreased APP expression at the cell surface (Malnar et al. Cholesterol 28-39 beta-secretase 1 Homo sapiens 141-146 22551668-2 2012 We previously reported that cholesterol accumulation in NPC-cells leads to cholesterol-dependent increased APP processing by beta-secretase (BACE1) and decreased APP expression at the cell surface (Malnar et al. Cholesterol 75-86 beta-secretase 1 Homo sapiens 141-146 22551668-5 2012 We hypothesized that increased formation of APP-CTFs and Abeta in NPC disease is due to cholesterol-mediated altered endocytic trafficking of APP and/or BACE1. Cholesterol 88-99 beta-secretase 1 Homo sapiens 153-158 22551668-7 2012 Moreover, we observed that NPC cells show cholesterol dependent sequestration and colocalization of APP and BACE1 within enlarged early/recycling endosomes which can lead to increased beta-secretase processing of APP. Cholesterol 42-53 beta-secretase 1 Homo sapiens 108-113 22551668-9 2012 Our findings suggest that increased cholesterol levels, such as in NPC disease and sporadic AD, may be the upstream effector that drives amyloidogenic APP processing characteristic for Alzheimer"s disease by altering endocytic trafficking of APP and BACE1. Cholesterol 36-47 beta-secretase 1 Homo sapiens 250-255 19074428-2 2009 A subset of BACE1 localizes to cholesterol-rich membrane microdomains, termed lipid rafts. Cholesterol 31-42 beta-secretase 1 Homo sapiens 12-17 21257714-0 2011 Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. Cholesterol 6-17 beta-secretase 1 Homo sapiens 62-67 21257714-5 2011 We show that less than 10 min after cholesterol exposure, Bace1-GFP/APP-mCherry proximity increases selectively at the membrane and APP relocalizes to raft domains, preceded by rapid endocytosis. Cholesterol 36-47 beta-secretase 1 Homo sapiens 58-63 21257714-6 2011 After longer cholesterol exposures, APP and Bace1 are found in proximity intracellularly. Cholesterol 13-24 beta-secretase 1 Homo sapiens 44-49 21257714-7 2011 We demonstrate that cholesterol loading does not increase Abeta production by having a direct impact on Bace1 catalytic activity but rather by altering the accessibility of Bace1 to its substrate, APP. Cholesterol 20-31 beta-secretase 1 Homo sapiens 173-178 19885829-3 2010 Recent evidence suggests that significant amounts of BACE1 and gamma-secretase components localize in the cholesterol-rich region of membranes known as lipid rafts, where A beta production occurs preferentially. Cholesterol 106-117 beta-secretase 1 Homo sapiens 53-58 21630010-0 2011 Activation of liver X receptor decreases BACE1 expression and activity by reducing membrane cholesterol levels. Cholesterol 92-103 beta-secretase 1 Homo sapiens 41-46 21630010-7 2011 Our results suggest that activation of LXR may decrease BACE1 expression and activity through a pathway associated with ABCA1-mediated reduction in membrane cholesterol levels. Cholesterol 157-168 beta-secretase 1 Homo sapiens 56-61 19074428-3 2009 BACE1 processing in raft microdomains of cultured cells and neurons was characterized in previous studies by disrupting the integrity of lipid rafts by cholesterol depletion. Cholesterol 152-163 beta-secretase 1 Homo sapiens 0-5 19199871-8 2009 Recent findings also indicate that a reduction of cellular cholesterol favours co-localization of BACE1 and APP in non-raft membrane domains and hinders generation of plasmin, an Abeta-degrading enzyme. Cholesterol 59-70 beta-secretase 1 Homo sapiens 98-103 16115865-0 2005 Lipids as modulators of proteolytic activity of BACE: involvement of cholesterol, glycosphingolipids, and anionic phospholipids in vitro. Cholesterol 69-80 beta-secretase 1 Homo sapiens 48-52 18374657-0 2008 Impact of cholesterol level upon APP and BACE proximity and APP cleavage. Cholesterol 10-21 beta-secretase 1 Homo sapiens 41-45 18374657-3 2008 However, there are controversial data whether APP and BACE can already interact on the cell surface dependent on the cholesterol level. Cholesterol 117-128 beta-secretase 1 Homo sapiens 54-58 18374657-6 2008 To analyze the impact of alterations in cholesterol level upon BACE-cleavage, we measured sAPP secretion. Cholesterol 40-51 beta-secretase 1 Homo sapiens 63-67 18374657-7 2008 Alteration of APP processing and BACE proximity by cholesterol might be explained by alterations in cell membrane fluidity. Cholesterol 51-62 beta-secretase 1 Homo sapiens 33-37 16303768-8 2006 PS1 and BACE are located in detergent-resistant membranes (DRMs), well structured membrane microdomains exhibiting high levels of cholesterol, and caveolin-1. Cholesterol 130-141 beta-secretase 1 Homo sapiens 8-12 16115865-6 2005 We have identified 3 groups of lipids that stimulate proteolytic activity of BACE: 1) neutral glycosphingolipids (cerebrosides), 2) anionic glycerophospholipids, and 3) sterols (cholesterol). Cholesterol 178-189 beta-secretase 1 Homo sapiens 77-84 35201266-3 2022 BACE1 is palmitoylated at its carboxyl-terminal region, which brings BACE1 to ordered, cholesterol-rich membrane microdomains (lipid rafts). Cholesterol 87-98 beta-secretase 1 Homo sapiens 0-5 11525745-10 2001 Finally, depletion of raft cholesterol abrogated association of Asp2 with the light membrane fraction. Cholesterol 27-38 beta-secretase 1 Homo sapiens 64-68 11525745-11 2001 These observations are consistent with the raft localization of APP processing and suggest that the partitioning of Asp2 into lipid rafts may underlie the cholesterol sensitivity of beta-amyloid production. Cholesterol 155-166 beta-secretase 1 Homo sapiens 116-120 34189821-5 2021 We hypothesize that there are multiple mechanisms responsible for segregating APP and BACE1 during transit through the Golgi, and that perturbation in Golgi morphology associated with Alzheimer"s disease, and or changes in cholesterol metabolism associated with Alzheimer"s disease risk factors, may lead to a loss of partitioning and enhanced Abeta production. Cholesterol 223-234 beta-secretase 1 Homo sapiens 86-91 15583033-5 2004 Much higher levels of BACE 1-APP colocalization is found in hippocampal membranes from AD patients or in rodent hippocampal neurons with a moderate reduction of membrane cholesterol. Cholesterol 170-181 beta-secretase 1 Homo sapiens 22-28 14501002-6 2003 In addition, the localization of the BACE complex to lipid rafts can explain previous findings that cholesterol and glycosylphosphatidylinositol (GPI)-anchored proteins are necessary for beta-secretase processing of APP. Cholesterol 100-111 beta-secretase 1 Homo sapiens 37-41 35201266-3 2022 BACE1 is palmitoylated at its carboxyl-terminal region, which brings BACE1 to ordered, cholesterol-rich membrane microdomains (lipid rafts). Cholesterol 87-98 beta-secretase 1 Homo sapiens 69-74 35201266-10 2022 A reduction of BACE1-dependent FRET between raft-targeting L10 probes and KCNQ2/3 channels by applying the cholesterol-extracting reagent methyl-beta-cyclodextrin (MbetaCD), raft-disrupting general anesthetics, or pharmacological inhibitors of palmitoylation, all supported the hypothesis of the palmitoylation-dependent and raft-specific localization of KCNQ2/3 channels. Cholesterol 107-118 beta-secretase 1 Homo sapiens 15-20