ArticleProceedings of the National Academy of Sciences of the United States of America2002
STAT1 deficiency unexpectedly and markedly exacerbates the pathophysiological actions of IFN-alpha in the central nervous system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Structural variant landscape provides insights into genome organisation and domestication in European seabass.BMC biology · 2025Article
- Lyophilized MSC-EVs attenuates COVID-19 pathogenesis by regulating the JAK/STAT pathway.Stem cell research & therapy · 2025Article
- Protein arginine methyltransferases as regulators of cellular stress.Experimental neurology · 2025Review
- Interleukin-6-induced neuroinflammation is exacerbated by subclinical levels of interferon-α.Frontiers in neuroscience · 2025Article
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- A Review on Role of Inflammation in Coronavirus Disease.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Differential expression of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in Alzheimer's disease and HIV-1 associated neurocognitive disorders.Scientific reports · 2023Article
- HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.Aging and disease · 2023Article
- Breaking down the cellular responses to type I interferon neurotoxicity in the brain.Frontiers in immunology · 2023Review
- Association of rare variants in genes of immune regulation with pediatric autoimmune CNS diseases.Journal of neurology · 2022Observational
- An aberrant STAT pathway is central to COVID-19.Cell death and differentiation · 2020Review
- Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus.Renal failure · 2020Article
- Rh-IFN-α attenuates neuroinflammation and improves neurological function by inhibiting NF-κB through JAK1-STAT1/TRAF3 pathway in an experimental GMH rat model.Brain, behavior, and immunity · 2019Article
- Type I interferon-regulated gene expression and signaling in murine mixed glial cells lacking signal transducers and activators of transcription 1 or 2 or interferon regulatory factor 9.The Journal of biological chemistry · 2017Article
- Protection from interferon-β-induced neuronal apoptosis through stimulation of muscarinic acetylcholine receptors coupled to ERK1/2 activation.British journal of pharmacology · 2016Article
- Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb-/- Microglia.PloS one · 2016Article
- Article
- Inflammatory impact of IFN-γ in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Stat1 negatively regulates immune-mediated injury with Anaplasma phagocytophilum infection.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Interferons, signal transduction pathways, and the central nervous system.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although signal transducer and activator of transcription 1 (STAT1) is an essential signaling molecule in many IFN-alpha-regulated processes, some biological responses to IFN-alpha can occur independently of STAT1. To establish the role of STAT1 in mediating the biological actions of IFN-alpha in the CNS, transgenic mice [termed glial fibrillary acidic protein (GFAP)-IFN-alpha] with astrocyte production of IFN-alpha were bred to be null for the STAT1 gene. Surprisingly, GFAP-IFN-alpha mice deficient for STAT1 developed earlier onset and more severe neurological disease with increased lethality compared with GFAP-IFN-alpha mice sufficient for STAT1. Whereas the brain of 2- to 3-month-old GFAP-IFN-alpha mice showed little, if any abnormality, the brain from GFAP-IFN-alpha mice deficient for STAT1 had severe neurodegeneration, inflammation, calcification with increased apoptosis, and glial activation. However, the cerebral expression of a number of IFN-regulated STAT1-dependent genes increased in GFAP-IFN-alpha mice but was reduced markedly in GFAP-IFN-alpha STAT1-null mice. Of many other signaling molecules examined, STAT3 alone was activated significantly in the brain of GFAP-IFN-alpha STAT1-null mice. Thus, in the absence of STAT1, alternative signaling pathways mediate pathophysiological actions of IFN-alpha in the living brain, giving rise to severe encephalopathy. Finally, STAT1 or a downstream component of the JAKSTAT pathway may protect against such IFN-alpha-mediated injury in the CNS.
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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.