ArticlePloS one2008
Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals.GeroScience · 2025Pooled it
- Reprogramming Neuroinflammation: Mitochondrial Targets and Immune Checkpoint Inhibitors in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.Cells · 2026Review
- Traumatic brain injury exacerbates mitochondrial dysfunction in APP/PS1 knock-in mice through time-dependent pathways.Experimental neurology · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- Role of Mitochondrial Calcium Dysregulation in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2025Review
- Traumatic brain injury exacerbates mitochondrial dysfunction in APP/PS1 knock-in mice through time-dependent pathways.bioRxiv : the preprint server for biology · 2025Article
- The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- 40 Hz light preserves synaptic plasticity and mitochondrial function in Alzheimer's disease model.Scientific reports · 2024Article
- Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer's Disease and Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Effect of β-amyloid on blood-brain barrier properties and function.Biophysical reviews · 2023Review
- Insights fromFrontiers in neuroscience · 2023Review
- Distinct Effects of Beta-Amyloid, Its Isomerized and Phosphorylated Forms on the Redox Status and Mitochondrial Functioning of the Blood-Brain Barrier Endothelium.International journal of molecular sciences · 2022Article
- Mitochondrial CaBiomedicines · 2022Review
- Amyloid Beta Oligomers-Induced CaBiomedicines · 2022Article
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of intracellular Ca(2+) homeostasis may underlie amyloid beta peptide (Abeta) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42) oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+) in neurons and promote mitochondrial Ca(2+) overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+) overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+) overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i) mitochondrial Ca(2+) overload underlies the neurotoxicity induced by Abeta oligomers and ii) inhibition of mitochondrial Ca(2+) overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.
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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.