ReviewBrain : a journal of neurology2024
How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?
Review in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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
22 citing papers in PubMed.
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.Neural regeneration research · 2026Article
- Development of a human iPSC-derived corticospinal tract-on-a-chip.Cell reports methods · 2026Article
- The Diagnostic Potential of Axon Excitability Is Consistent Across Hand Muscles in Amyotrophic Lateral Sclerosis.Muscle & nerve · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Human stem cell-derived neurons establish functional inhibitory-excitatory cortical circuits in a chimeric transplantation model.Scientific reports · 2026Article
- Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model.PloS one · 2026Article
- Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.Brain communications · 2026Review
- Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.International journal of molecular sciences · 2025Article
- Evaluation of a New Riluzole-Based Compound VA945 on Sodium and Potassium Conductances Expressed by SH-SY5Y- Derived Neurons.Journal of neurochemistry · 2025Article
- Network Dysfunction Precedes Neurodegeneration in a dox-Regulatable TDP-43 Mouse Model of ALS-FTD.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Cytoskeletal disruption-induced calcium dysregulation drives cell death in anti-IgLON5 disease.Redox biology · 2025Article
- Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis.Annals of neurology · 2025Article
- Lethal Interactions of neuronal networks in epilepsy mediated by both synaptic and volume transmission indicate approaches to prevention.Progress in neurobiology · 2025Review
- Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.Muscle & nerve · 2025Review
- A stress-dependent TDP-43 SUMOylation program preserves neuronal function.Molecular neurodegeneration · 2025Article
- Review
- The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations.Brain sciences · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the 'dying forward' excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the 'dying forward' excitotoxicity hypothesis and the failure of therapies that target neuronal activation. One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the 'dying forward' excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis. We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.
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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 Socratic graph.