ArticleCell death & disease2011
A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Advances in Stem Cell Therapy for Huntington's Disease: A Comprehensive Literature Review.Cells · 2025Pooled it
- Understanding the psycho-neuro-endocrine-immunology pathways in glaucoma and their modulation by mindfulness meditation.Indian journal of ophthalmology · 2026Review
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Eugenol regulates ferroptosis through Mfn2/SLC7A11/GPX4 pathway to alleviate glutamate excitotoxicity damage in glaucoma.Molecular and cellular biochemistry · 2026Article
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Neurodegenerative and Glial Physiology in Diabetic Retinopathy: Dissociated Effects of Forskolin on Neuronal Survival and Glial Activation.Biomedicines · 2026Article
- Dual targeting of iNOS and Src tyrosine kinase as a superior therapeutic strategy against soman-induced long-term neurotoxicity: multimodal biomarker, imaging, and neurobehavioral outcome analyses.Acta neuropathologica communications · 2026Article
- Acupuncture-induced HSP70 upregulation in neuroprotection: mitochondrial and anti-apoptotic mechanisms.American journal of translational research · 2026Review
- Article
- OPA1 Enhances Microglial Amyloid-β Clearance and Alleviates Cognitive Impairments in an Alzheimer's Disease Model.Aging and disease · 2025Article
- Glial Cells in Spinal Muscular Atrophy: Speculations on Non-Cell-Autonomous Mechanisms and Therapeutic Implications.Neurology international · 2025Review
- Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells.Acta neuropathologica communications · 2025Article
- Prenatal modulation of NADPH-oxidase reverses the deranged GABA switch and rescues behavioral deficits in valproate ASD rat model.Frontiers in pharmacology · 2025Article
- System Xc-pathway as a potential regulatory target in neurological disorders.Frontiers in pharmacology · 2025Review
- Serum neuronal, glial and mitochondrial markers in autosomal dominant optic atrophy and Leber hereditary optic neuropathy.Brain communications · 2025Article
- A Reduction in Mitophagy Is Associated with Glaucomatous Neurodegeneration in Rodent Models of Glaucoma.International journal of molecular sciences · 2024Article
- ACognitive neurodynamics · 2024Article
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.Brain : a journal of neurology · 2024Article
72 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
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1(enu/+) mice show a slow progressive loss of RGCs, activation of astroglia and microglia, and pronounced mitochondrial fission in optic nerve heads as found by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the retina of Opa1(enu/+) mice was significantly increased as determined by western blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was significantly decreased, the apoptotic pathway was activated as Bax was increased, and phosphorylated Bad and BcL-xL were decreased. Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics.
Indexed as
Identifiers
What 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.