ArticleProceedings of the National Academy of Sciences of the United States of America2016
Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Impaired nucleocytoplasmic transport in SOD1-mediated ALS.Molecular neurodegeneration · 2026Article
- siRNA for REST ameliorates symptoms in ALS mice and serum REST predicts disease prognosis and survival in ALS patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Macrophage migration inhibitory factor: Exploring physiological roles and comparing health benefits against oncogenic and autoimmune risks (Review).International journal of molecular medicine · 2025Review
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- Genetic background variation impacts microglial heterogeneity and disease progression in amyotrophic lateral sclerosis model mice.iScience · 2024Article
- 4-Phenylbutyric Acid (4-PBA) Derivatives Prevent SOD1 Amyloid Aggregation In Vitro with No Effect on Disease Progression in SOD1-ALS Mice.International journal of molecular sciences · 2022Article
- MIF homolog d-dopachrome tautomerase (D-DT/MIF-2) does not inhibit accumulation and toxicity of misfolded SOD1.Scientific reports · 2022Article
- Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.Cell death & disease · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- A pilot reverse virtual screening study suggests toxic exposures caused long-term epigenetic changes in Gulf War Illness.Computational and structural biotechnology journal · 2022Article
- Early upregulation of cytosolic phospholipase AJournal of neuroinflammation · 2021Article
- The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer's Disease.Cells · 2021Review
- Macrophage migration inhibitory factor in Nodding syndrome.PLoS neglected tropical diseases · 2021Article
- All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration.Cells · 2021Review
- Article
- ALS-Related Mutant SOD1 Aggregates Interfere with Mitophagy by Sequestering the Autophagy Receptor Optineurin.International journal of molecular sciences · 2020Article
- Molecular and pharmacological chaperones for SOD1.Biochemical Society transactions · 2020Review
- The Dichotomic Role of Macrophage Migration Inhibitory Factor in Neurodegeneration.International journal of molecular sciences · 2020Review
- The Role of Macrophage Migration Inhibitory Factor in Alzheimer's Disease: Conventionally Pathogenetic or Unconventionally Protective?Molecules (Basel, Switzerland) · 2020Review
- AAV2/9-mediated overexpression of MIF inhibits SOD1 misfolding, delays disease onset, and extends survival in mouse models of ALS.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons in the brain and spinal cord. It has been suggested that the toxicity of mutant SOD1 results from its misfolding and accumulation on the cytoplasmic faces of intracellular organelles, including the mitochondria and endoplasmic reticulum (ER) of ALS-affected tissues. Recently, macrophage migration inhibitory factor (MIF) was shown to directly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membranes, but the role of endogenous MIF in modulating SOD1 misfolding in vivo remains unknown. To elucidate this role, we bred MIF-deficient mice with SOD1(G85R) mice, which express a dismutase-inactive mutant of SOD1 and are considered a model of familial ALS. We found that the accumulation of misfolded SOD1, its association with mitochondrial and ER membranes, and the levels of sedimentable insoluble SOD1 aggregates were significantly higher in the spinal cords of SOD1(G85R)-MIF(-/-) mice than in their SOD1(G85R)-MIF(+/+) littermates. Moreover, increasing MIF expression in neuronal cultures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell death. In contrast, the complete elimination of endogenous MIF accelerated disease onset and late disease progression and shortened the lifespan of the SOD1(G85R) mutant mice. These findings indicate that MIF plays a significant role in the folding and misfolding of SOD1 in vivo, and they have implications for the potential therapeutic role of up-regulating MIF within the nervous system to modulate the selective accumulation of misfolded SOD1.
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