ArticleFrontiers in neuroscience2015
Hypoxia Affects Neprilysin Expression Through Caspase Activation and an APP Intracellular Domain-dependent Mechanism.
Article in Frontiers in neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Paroxysmal slow wave events are associated with cognitive impairment in patients with obstructive sleep apnea.Alzheimer's research & therapy · 2022Trial
- Late-onset alzheimer's disease, atherosclerosis, and cerebrovascular disease. A complex relationship too often neglected: a narrative review.Aging clinical and experimental research · 2025Review
- Flow-Cytometric Quantification of Urine Kidney Epithelial Cells Specifically Reflects Tubular Damage in Acute Kidney Diseases.Kidney international reports · 2025Article
- Exploring the role of HIF-1α on pathogenesis in Alzheimer's disease and potential therapeutic approaches.Inflammopharmacology · 2025Review
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- Review
- Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Article
- HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia.International journal of molecular sciences · 2022Article
- Caspase Inhibition Restores NEP Expression and Rescues Olfactory Deficit in Rats Caused by Prenatal Hypoxia.Journal of molecular neuroscience : MN · 2022Article
- Review
- Oxygen Sensing and Signaling in Alzheimer's Disease: A Breathtaking Story!Cellular and molecular neurobiology · 2022Review
- Review
- The Association between Neprilysin gene polymorphisms and Alzheimer's disease in Tibetan population.Brain and behavior · 2021Article
- Neprilysin expression and functions in development, ageing and disease.Mechanisms of ageing and development · 2020Review
- Article
- Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy.British journal of pharmacology · 2019Review
- Hypoxia and aging.Experimental & molecular medicine · 2019Review
- Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia.Neurochemical research · 2019Article
- What are the links between hypoxia and Alzheimer's disease?Neuropsychiatric disease and treatment · 2019Article
- Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties.BMC neuroscience · 2018Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While gene mutations in the amyloid precursor protein (APP) and the presenilins lead to an accumulation of the amyloid β-peptide (Aβ) in the brain causing neurodegeneration and familial Alzheimer's disease (AD), over 95% of all AD cases are sporadic. Despite the pathologies being indistinguishable, relatively little is known about the mechanisms affecting generation of Aβ in the sporadic cases. Vascular disorders such as ischaemia and stroke are well established risk factors for the development of neurodegenerative diseases and systemic hypoxic episodes have been shown to increase Aβ production and accumulation. We have previously shown that hypoxia causes a significant decrease in the expression of the major Aβ-degrading enzyme neprilysin (NEP) which might deregulate Aβ clearance. Aβ itself is derived from the transmembrane APP along with several other biologically active metabolites including the C-terminal fragment (CTF) termed the APP intracellular domain (AICD), which regulates the expression of NEP and some other genes in neuronal cells. Here we show that in hypoxia there is a significantly increased expression of caspase-3, 8, and 9 in human neuroblastoma NB7 cells, which can degrade AICD. Using chromatin immunoprecipitation we have revealed that there was also a reduction of AICD bound to the NEP promoter region which underlies the decreased expression and activity of the enzyme under hypoxic conditions. Incubation of the cells with a caspase-3 inhibitor Z-DEVD-FMK could rescue the effect of hypoxia on NEP activity protecting the levels of AICD capable of binding the NEP promoter. These data suggest that activation of caspases might play an important role in regulation of NEP levels in the brain under pathological conditions such as hypoxia and ischaemia leading to a deficit of Aβ clearance and increasing the risk of development of AD.
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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 Socratic graph.