ArticleMolecular medicine (Cambridge, Mass.)2012
Neuroprotective effects of toll-like receptor 4 antagonism in spinal cord cultures and in a mouse model of motor neuron degeneration.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 74 citations in OpenAlex.
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- Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.Biomolecules · 2024Article
- Stalling the Course of Neurodegenerative Diseases: Could Cyanobacteria Constitute a New Approach toward Therapy?Biomolecules · 2023Review
- Role of neuroinflammation in neurodegeneration development.Signal transduction and targeted therapy · 2023Review
- Early Signs of Neuroinflammation in the Postnatal Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.Cellular and molecular neurobiology · 2023Article
- Potential therapeutic strategies for myocardial infarction: the role of Toll-like receptors.Immunologic research · 2022Review
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- Review of Cyanotoxicity Studies Based on Cell Cultures.Journal of toxicology · 2022Review
- Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2021Review
- Little Helpers or Mean Rogue-Role of Microglia in Animal Models of Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2021Review
- Tlr2/4 Double Knockout Attenuates the Degeneration of Primary Auditory Neurons: Potential Mechanisms From Transcriptomic Perspectives.Frontiers in cell and developmental biology · 2021Article
- CXCL13/CXCR5 signalling is pivotal to preserve motor neurons in amyotrophic lateral sclerosis.EBioMedicine · 2020Article
- Absence of Receptor for Advanced Glycation End Product (RAGE) Reduces Inflammation and Extends Survival in the hSOD1Molecular neurobiology · 2020Article
- Microglia-targeting nanotherapeutics for neurodegenerative diseases.APL bioengineering · 2020Article
- Insights into the Therapeutic Potential of Glucocorticoid Receptor Modulators for Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- TLR4-Targeting Therapeutics: Structural Basis and Computer-Aided Drug Discovery Approaches.Molecules (Basel, Switzerland) · 2020Review
- Therapeutic blockade of HMGB1 reduces early motor deficits, but not survival in the SOD1Journal of neuroinflammation · 2019Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustained inflammatory reactions are common pathological events associated with neuron loss in neurodegenerative diseases. Reported evidence suggests that Toll-like receptor 4 (TLR4) is a key player of neuroinflammation in several neurodegenerative diseases. However, the mechanisms by which TLR4 mediates neurotoxic signals remain poorly understood. We investigated the role of TLR4 in in vitro and in vivo settings of motor neuron degeneration. Using primary cultures from mouse spinal cords, we characterized both the proinflammatory and neurotoxic effects of TLR4 activation with lipopolysaccharide (activation of microglial cells, release of proinflammatory cytokines and motor neuron death) and the protective effects of a cyanobacteria-derived TLR4 antagonist (VB3323). With the use of TLR4-deficient cells, a critical role of the microglial component with functionally active TLR4 emerged in this setting. The in vivo experiments were carried out in a mouse model of spontaneous motor neuron degeneration, the wobbler mouse, where we preliminarily confirmed a protective effect of TLR4 antagonism. Compared with vehicle- and riluzole-treated mice, those chronically treated with VB3323 showed a decrease in microglial activation and morphological alterations of spinal cord neurons and a better performance in the paw abnormality and grip-strength tests. Taken together, our data add new understanding of the role of TLR4 in mediating neurotoxicity in the spinal cord and suggest that TLR4 antagonists could be considered in future studies as candidate protective agents for motor neurons in degenerative diseases.
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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.