ArticleScientific reports2016
High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 73 citations in OpenAlex.
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- The Effects of Coenzyme Q10 Supplementation on the Contrast Sensitivity Score, Biomarkers of Oxidative Stress, Inflammation, and β-Secretase Activity in the Blood and the Correlation Among these Factors in Diabetic Retinopathy Patients; Clinical Trial.Advanced pharmaceutical bulletin · 2026Article
- Intranasal Formaldehyde Exposure Induces RAGE-Mediated Alteration of the ADAM10/BACE1 Expression Balance and Amyloid Deposition.Biomedicines · 2026Article
- Transglutaminase-2 Promotes Microglial Synaptic Phagocytosis and Ameliorates Epileptic Seizures by Inhibiting ABCA1 Ubiquitination.CNS neuroscience & therapeutics · 2025Article
- Unraveling novel mechanisms of ATP-Binding cassette (ABC) transporter in insulin Resistance-induced amyloidogenesis.Metabolic brain disease · 2025Review
- BACE1 at the crossroads of a vicious circle between Alzheimer's disease and diabetes mellitus.Frontiers in dementia · 2025Review
- Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer's Disease: Beneficial or Detrimental?Antioxidants (Basel, Switzerland) · 2024Review
- The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer's disease.Experimental & molecular medicine · 2024Review
- Insulin resistance as the molecular link between diabetes and Alzheimer's disease.World journal of diabetes · 2024Review
- Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells.Molecular biology reports · 2024Article
- The relationship between hypoxia and Alzheimer's disease: an updated review.Frontiers in aging neuroscience · 2024Review
- High glucose induced HIF-1α/TREK1 expression and myometrium relaxation during pregnancy.Frontiers in endocrinology · 2023Article
- Genome-wide placental DNA methylations in fetal overgrowth and associations with leptin, adiponectin and fetal growth factors.Clinical epigenetics · 2022Article
- Effect of liver X receptor agonist TO901317 on cognitive function in APP/PS1 double transgenic mice with AlzheimerZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Magnesium-L-threonate exhibited a neuroprotective effect against oxidative stress damage in HT22 cells and Alzheimer's disease mouse model.World journal of psychiatry · 2022Article
- Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target.Journal of biochemical and molecular toxicology · 2021Review
- The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1α expression, associated with regulation of BACE1 and Liver X Receptor α (LXRα). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate Aβ secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization, leading to Aβ production and apoptosis of SK-N-MC.
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