ArticleCNS neuroscience & therapeutics2013
Hypoxia-triggered m-calpain activation evokes endoplasmic reticulum stress and neuropathogenesis in a transgenic mouse model of Alzheimer's disease.
Article in CNS neuroscience & therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Impact of hypoxia on the hippocampus: A review.Medicine · 2025Review
- Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis.Antioxidants (Basel, Switzerland) · 2025Article
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Extracellular CIRP Induces Calpain Activation in Neurons via PLC-IPMolecular neurobiology · 2023Article
- Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy?Biomolecules · 2023Review
- ER stress and UPR in Alzheimer's disease: mechanisms, pathogenesis, treatments.Cell death & disease · 2022Review
- GABA Receptor Agonists Protect From Excitotoxic Damage Induced by AMPA in Oligodendrocytes.Frontiers in pharmacology · 2022Article
- Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.Frontiers in cellular neuroscience · 2022Review
- Selenoprotein K deficiency-induced apoptosis: A role for calpain and the ERS pathway.Redox biology · 2021Article
- Neurosteroids and oxysterols as potential therapeutic agents for glaucoma and Alzheimer's disease.Neuropsychiatry · 2018Article
- Article
- Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation.Biochimica et biophysica acta · 2015Article
- Sulforaphane ameliorates neurobehavioral deficits and protects the brain from amyloid β deposits and peroxidation in mice with Alzheimer-like lesions.American journal of Alzheimer's disease and other dementias · 2015Article
- Endoplasmic reticulum stress: relevance and therapeutics in central nervous system diseases.Molecular neurobiology · 2015Review
- CD36 upregulation mediated by intranasal LV-NRF2 treatment mitigates hypoxia-induced progression of Alzheimer's-like pathogenesis.Antioxidants & redox signaling · 2014Article
- Epigenetic modifications of chronic hypoxia-mediated neurodegeneration in Alzheimer's disease.Translational neurodegeneration · 2014Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious studies have demonstrated that endoplasmic reticulum (ER) stress is activated in Alzheimer's disease (AD) brains. ER stress-triggered unfolded protein response (UPR) leads to tau phosphorylation and neuronal death.
aimsIn this study, we tested the hypothesis that hypoxia-induced m-calpain activation is involved in ER stress-mediated AD pathogenesis.
methodWe employed a hypoxic exposure in APP/PS1 transgenic mice and SH-SY5Y cells overexpressing human Swedish mutation APP (APPswe).
resultsWe observed that hypoxia impaired spatial learning and memory in the APP/PS1 mouse. In the transgenic mouse brain, hypoxia increased the UPR, upregulated apoptotic signaling, enhanced the activation of calpain and glycogen synthase kinase-3β (GSK3β), and increased tau hyperphosphorylation and β-amyloid deposition. In APPswe cells, m-calpain silencing reduced hypoxia-induced cellular dysfunction and resulted in suppression of GSK3β activation, ER stress and tau hyperphosphorylation reduction as well as caspase pathway suppression.
conclusionThese findings demonstrate that hypoxia-induced abnormal calpain activation may increase ER stress-induced apoptosis in AD pathogenesis. In contrast, a reduction in the expression of the m-calpain isoform reduces ER stress-linked apoptosis that is triggered by hypoxia. These findings suggest that hypoxia-triggered m-calpain activation is involved in ER stress-mediated AD pathogenesis. m-calpain is a potential target for AD therapeutics.
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