ArticleDisease models & mechanisms2015
Identifying the primary site of pathogenesis in amyotrophic lateral sclerosis - vulnerability of lower motor neurons to proximal excitotoxicity.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03326622 (The Role of Moderate Aerobic Exercise as Determined by Cardiopulmonary Exercise Testing in ALS), which is not on this map. Cited by 24 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.
The Role of Moderate Aerobic Exercise as Determined by Cardiopulmonary Exercise Testing in ALS
Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Microfluidic co-culture system for synaptically segregated neural networks to explore astrocyte-driven neural pathology.Microsystems & nanoengineering · 2026Article
- Modeling ALS in a dish: how organoids are transforming research.Frontiers in medicine · 2026Review
- Targeting CRABP1 Signalosomes in Managing Neurodegeneration.Biomolecules · 2025Review
- Article
- Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo.Disease models & mechanisms · 2023Article
- Synaptic Dysfunction and Plasticity in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Review
- Estrogen Enhances Dendrite Spine Function and Recovers Deficits in Neuroplasticity in the prpTDP-43Molecular neurobiology · 2022Article
- Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2022Review
- Current Progress in the Creation, Characterization, and Application of Human Stem Cell-derived in Vitro Neuromuscular Junction Models.Stem cell reviews and reports · 2022Review
- ALS/FTD: Evolution, Aging, and Cellular Metabolic Exhaustion.Frontiers in neurology · 2022Article
- Microglia autophagy in ischemic stroke: A double-edged sword.Frontiers in immunology · 2022Review
- Modeling Neurodegenerative Diseases UsingFrontiers in bioengineering and biotechnology · 2022Review
- Influence of Housing Systems on Physical, Emotional, and Cognitive Functions with Aging in DBA/2CrSlc Mice.Animals : an open access journal from MDPI · 2020Article
- Article
- Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function.Disease models & mechanisms · 2019Article
- Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis.NeuroImage. Clinical · 2019Article
- Reduced Excitability and Increased Neurite Complexity of Cortical Interneurons in a Familial Mouse Model of Amyotrophic Lateral Sclerosis.Frontiers in cellular neuroscience · 2018Article
- Challenges and Future Prospects on 3DFrontiers in bioengineering and biotechnology · 2018Review
- The Role of Moderate Aerobic Exercise as Determined by Cardiopulmonary Exercise Testing in ALS.Neurology research international · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a desperate need for targeted therapeutic interventions that slow the progression of amyotrophic lateral sclerosis (ALS). ALS is a disorder with heterogeneous onset, which then leads to common final pathways involving multiple neuronal compartments that span both the central and peripheral nervous system. It is believed that excitotoxic mechanisms might play an important role in motor neuron death in ALS. However, little is known about the mechanisms by which excitotoxicity might lead to the neuromuscular junction degeneration that characterizes ALS, or about the site at which this excitotoxic cascade is initiated. Using a novel compartmentalised model of site-specific excitotoxin exposure in lower motor neurons in vitro, we found that spinal motor neurons are vulnerable to somatodendritic, but not axonal, excitotoxin exposure. Thus, we developed a model of somatodendritic excitotoxicity in vivo using osmotic mini pumps in Thy-1-YFP mice. We demonstrated that in vivo cell body excitotoxin exposure leads to significant motor neuron death and neuromuscular junction (NMJ) retraction. Using confocal real-time live imaging of the gastrocnemius muscle, we found that NMJ remodelling preceded excitotoxin-induced NMJ degeneration. These findings suggest that excitotoxicity in the spinal cord of individuals with ALS might result in a die-forward mechanism of motor neuron death from the cell body outward, leading to initial distal plasticity, followed by subsequent pathology and degeneration.
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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.