ArticleBiochimica et biophysica acta2012
Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: implications for cellular Aβ metabolism.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- NUMB in Endometrial Pathology: From Adenomyosis Expression Patterns to Endometrial Cancer Survival Implications.Current issues in molecular biology · 2025Article
- Integrative bioinformatics and machine learning identify iron metabolism genes MAP4, GPT, and HIRIP3 as diagnostic biomarkers and therapeutic targets in Alzheimer's disease.Frontiers in cellular neuroscience · 2025Article
- Review
- Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.International journal of molecular sciences · 2024Review
- The novel anti-colitic effect of β-adrenergic receptorsFrontiers in pharmacology · 2022Article
- Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4.iScience · 2021Article
- Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma.International journal of oncology · 2021Article
- 2',3'-Cyclic-nucleotide 3'-phosphodiesterase contributes to epithelial-mesenchymal transition of lens epithelial cells through the notch signalling pathway.Cell proliferation · 2019Article
- Chronic Hippocampal Expression of Notch Intracellular Domain Induces Vascular Thickening, Reduces Glucose Availability, and Exacerbates Spatial Memory Deficits in a Rat Model of Early Alzheimer.Molecular neurobiology · 2018Article
- The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice.International journal of molecular sciences · 2018Article
- Notch1 hallmarks fibrillary depositions in sporadic Alzheimer's disease.Acta neuropathologica communications · 2016Article
- Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer's disease-related pathologies in APPswe/PS1dE9 transgenic mice.Journal of biomedical science · 2016Article
- Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis.Reproduction (Cambridge, England) · 2015Article
- Notch Intracellular Domain (NICD) Suppresses Long-Term Memory Formation in Adult Drosophila Flies.Cellular and molecular neurobiology · 2015Article
- Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice.Acta pharmacologica Sinica · 2015Article
- Alteration of mitochondrial proteome due to activation of Notch1 signaling pathway.The Journal of biological chemistry · 2014Article
- Regulation of insulin degrading enzyme activity by obesity-associated factors and pioglitazone in liver of diet-induced obese mice.PloS one · 2014Article
- Genome-wide significant localization for working and spatial memory: Identifying genes for psychosis using models of cognition.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2014Article
- Article
- Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Cerebral amyloid β (Aβ) accumulation is pathogenically associated with sporadic Alzheimer's disease (SAD). BACE-1 is involved in Aβ generation while insulin-degrading enzyme (IDE) partakes in Aβ proteolytic clearance. Vulnerable regions in AD brains show increased BACE-1 protein levels and enzymatic activity while the opposite occurs with IDE. Another common feature in SAD brains is Notch1 overexpression. Here we demonstrate an increase in mRNA levels of Hey-1, a Notch target gene, and a decrease of IDE transcripts in the hippocampus of SAD brains as compared to controls. Transient transfection of Notch intracellular domain (NICD) in N2aSW cells, mouse neuroblastoma cells (N2a) stably expressing human amyloid precursor protein (APP) Swedish mutation, reduce IDE mRNA levels, promoting extracellular Aβ accumulation. Also, NICD, HES-1 and Hey-1 overexpression result in decreased IDE proximal promoter activity. This effect was mediated by 2 functional sites located at -379/-372 and -310-303 from the first translation start site in the -575/-19 (556 bp) fragment of IDE proximal promoter. By site-directed mutagenesis of the IDE promoter region we reverted the inhibitory effect mediated by NICD transfection suggesting that these sites are indeed responsible for the Notch-mediated inhibition of the IDE gene expression. Intracranial injection of the Notch ligand JAG-1 in Tg2576 mice, expressing the Swedish mutation in human APP, induced overexpression of HES-1 and Hey-1 and reduction of IDE mRNA levels, respectively. Our results support our theory that a Notch-dependent IDE transcriptional modulation may impact on Aβ metabolism providing a functional link between Notch signaling and the amyloidogenic pathway in SAD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.