ArticleAnnals of clinical and translational neurology2014
Laquinimod reduces neuroaxonal injury through inhibiting microglial activation.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 90 citations in OpenAlex.
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- Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Role of Microglial Cells in the Pathophysiology of MS: Synergistic or Antagonistic?International journal of molecular sciences · 2023Review
- New insight on microglia activation in neurodegenerative diseases and therapeutics.Frontiers in neuroscience · 2023Review
- Cathepsin-B inhibitor CA-074 attenuates retinopathy and optic neuritis in experimental autoimmune encephalomyelitis induced in SJL/J mice.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Single-cell and spatial RNA sequencing identify perturbators of microglial functions with aging.Nature aging · 2022Article
- Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets.Cellular and molecular life sciences : CMLS · 2022Review
- Manipulating Macrophage/Microglia Polarization to Treat Glioblastoma or Multiple Sclerosis.Pharmaceutics · 2022Review
- A DistinctCells · 2022Article
- Targeting immune cell metabolism in kidney diseases.Nature reviews. Nephrology · 2021Review
- Harnessing the Benefits of Neuroinflammation: Generation of Macrophages/Microglia with Prominent Remyelinating Properties.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by microglia.Nature neuroscience · 2021Article
- Aryl Hydrocarbon Receptor Activation in Astrocytes by Laquinimod Ameliorates Autoimmune Inflammation in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Microglia: A Potential Drug Target for Traumatic Axonal Injury.Neural plasticity · 2021Review
- Laquinimod Modulates Human Astrocyte Function and Dampens Astrocyte-Induced Neurotoxicity during Inflammation.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLaquinimod is an emerging oral medication for multiple sclerosis (MS) that reduces brain atrophy and progression of disability in two Phase III clinical trials. The mechanism of these effects is unclear. Persistent activation of microglia occurs in MS and contributes to injury. Thus, we investigated whether laquinimod alters properties of microglia in culture and in experimental autoimmune encephalomyelitis (EAE), and whether this reduces neurodegeneration.
methodsMicroglia were cultured from human brains. EAE was induced in mice.
resultsThe activation of human microglia increased levels of several pro- and anti-inflammatory cytokines and these elevations were attenuated by pretreatment with laquinimod. Laquinimod prevented the decline in activated microglia of miR124a, a microRNA implicated in maintaining microglia quiescence, and reduced the activity of several signaling pathways (Jun-N-terminal kinase, ribosomal S6 kinase, and AKT/protein kinase B) in activated microglia. In EAE, axonal injury correlated with accumulation of microglia/macrophages in the spinal cord. EAE mice treated with laquinimod before onset of clinical signs subsequently had reduced microglia/macrophage density and axonal injury. Remarkably, when laquinimod treatment was initiated well into the disease course, the progressive demyelination, and axonal loss was halted. Besides inflammatory molecules associated with microglia, the level of inducible nitric oxide (NO) synthase capable of producing free radical toxicity was attenuated by laquinimod in EAE mice. Finally, in coculture where microglia activation caused neuronal death, laquinimod decreased NO levels, and neurotoxicity.
interpretationLaquinimod is a novel inhibitor of microglial activation that lowers microglia-induced neuronal death in culture and axonal injury/loss in EAE.
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.