ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 171 citations in OpenAlex.
- Genomic and proteomic conversion of brain ischemia to Alzheimer's disease.Frontiers in cell and developmental biology · 2026Review
- A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes.Cell death & disease · 2025Article
- Factors Contributing to Resistance to Ischemia-Reperfusion Injury in Olfactory Mitral Cells.International journal of molecular sciences · 2025Review
- Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.eLife · 2024Review
- A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model.Current Alzheimer research · 2024Review
- Mechanistic insights of neuronal calcium and IPEuropean biophysics journal : EBJ · 2023Article
- Impairment of Ceramide-Mediated Endothelial Instant Membrane Resealing During Diabetes Mellitus.Frontiers in physiology · 2022Article
- Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?European review for medical and pharmacological sciences · 2020Article
- Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation.PloS one · 2018Article
- Presenilin1/γ-secretase protects neurons from glucose deprivation-induced death by regulating miR-212 and PEA15.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Endoplasmic reticulum stress and inflammation in the central nervous system.Molecular neurodegeneration · 2017Review
- Contribution of redox-dependent activation of endothelial Nlrp3 inflammasomes to hyperglycemia-induced endothelial dysfunction.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Presenilin 1 promotes trypsin-induced neuroprotection via the PAR2/ERK signaling pathway. Effects of presenilin 1 FAD mutations.Neurobiology of aging · 2016Article
- Susceptibility to focal and global brain ischemia of Alzheimer mice displaying aβ deposits: effect of immunoglobulin.Aging and disease · 2014Article
- Regulated necrosis: the expanding network of non-apoptotic cell death pathways.Nature reviews. Molecular cell biology · 2014Review
- Sporadic Alzheimer's disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer's disease genes.Molecular neurobiology · 2013Review
- Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors.Neurobiology of aging · 2013Article
- Protective effects of incensole acetate on cerebral ischemic injury.Brain research · 2012Article
- Orais and STIMs: physiological mechanisms and disease.Journal of cellular and molecular medicine · 2012Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Studies of cultured neural cells suggest that PS1 mutations result in perturbed cellular calcium homeostasis and may thereby render neurons vulnerable to apoptosis. In light of evidence that metabolic impairment plays a role in AD, that cerebral ischemia may be a risk factor for AD, and that individuals with AD have increased morbidity and mortality after stroke, we examined the impact of a PS1 mutation on neuronal vulnerability to ischemic injury. We report that the extent of brain injury after focal cerebral ischemia reperfusion is increased, and behavioral outcome is worsened, in PS1 mutant knock-in mice compared to wild-type mice. Cultured cortical neurons from PS1 mutant mice exhibit increased vulnerability to glucose deprivation and chemical hypoxia compared to their wild-type counterparts. Calcium imaging studies demonstrated enhanced elevation of intracellular calcium levels after glucose deprivation and chemical hypoxia in neurons from PS1 mutant mice. Agents that block calcium release from IP(3)- and ryanodine-sensitive stores (xestospongin and dantrolene, respectively) protected against the endangering action of the PS1 mutation. Our data suggest that presenilin mutations may promote neuronal degeneration in AD by increasing the sensitivity of neurons to age-related ischemia-like conditions. The data further suggest that drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients.
Indexed as
Identifiers
10662826PMC6772370W1950983788What OpenQuestion holds
Registered trials
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.