ArticleJournal of neuroinflammation2021
A novel phosphoproteomic landscape evoked in response to type I interferon in the brain and in glial cells.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting MAPK-dependent pathways to modulate reactive astrocyte pathology in neurodegeneration.Communications biology · 2026Article
- Learning the PTM code through a coarse-to-fine mechanism-aware framework.Nature communications · 2026Article
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Cross-species transcriptomic evidence for peripheral-central immune crosstalk in atopic dermatitis.Frontiers in immunology · 2026Article
- Type I interferon signalling and interferon-responsive microglia in health and disease.The FEBS journal · 2025Review
- Unveiling the role of PSD95 phosphorylation after traumatic brain injury: insights from phosphoproteomic analysis.BMC neurology · 2025Article
- Single-cell ultra-high-throughput multiplexed chromatin and RNA profiling reveals gene regulatory dynamics.Nature methods · 2025Article
- Post-translational modification prediction via prompt-based fine-tuning of a GPT-2 model.Nature communications · 2024Article
- The brain microvasculature is a primary mediator of interferon-α neurotoxicity in human cerebral interferonopathies.Immunity · 2024Article
- The type-I interferon response potentiates seeded tau aggregation and exacerbates tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Interferon-α receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy.The Journal of clinical investigation · 2024Article
- Breaking down the cellular responses to type I interferon neurotoxicity in the brain.Frontiers in immunology · 2023Review
- Analysis of Age-Dependent Transcriptomic Changes in Response to Intracerebral Hemorrhage in Mice.Frontiers in molecular neuroscience · 2022Article
- Phosphoregulation of the septin cytoskeleton in neuronal development and disease.Cytoskeleton (Hoboken, N.J.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundType I interferons (IFN-I) are key responders to central nervous system infection and injury and are also increased in common neurodegenerative diseases. Their effects are primarily mediated via transcriptional regulation of several hundred interferon-regulated genes. In addition, IFN-I activate several kinases including members of the MAPK and PI3K families. Yet, how changes to the global protein phosphoproteome contribute to the cellular response to IFN-I is unknown.
methodsThe cerebral phosphoproteome of mice with brain-targeted chronic production of the IFN-I, IFN-α, was obtained. Changes in phosphorylation were analyzed by ontology and pathway analysis and kinase enrichment predictions. These were verified by phenotypic analysis, immunohistochemistry and immunoblots. In addition, primary murine microglia and astrocytes, the brain's primary IFN-I-responding cells, were acutely treated with IFN-α and the global phosphoproteome was similarly analyzed.
resultsWe identified widespread protein phosphorylation as a novel mechanism by which IFN-I mediate their effects. In our mouse model for IFN-I-induced neurodegeneration, protein phosphorylation, rather than the proteome, aligned with the clinical hallmarks and pathological outcome, including impaired development, motor dysfunction and seizures. In vitro experiments revealed extensive and rapid IFN-I-induced protein phosphorylation in microglia and astrocytes. Response to acute IFN-I stimulation was independent of gene expression and mediated by a small number of kinase families. The changes in the phosphoproteome affected a diverse range of cellular processes and functional analysis suggested that this response induced an immediate reactive state and prepared cells for subsequent transcriptional responses.
conclusionsOur studies reveal a hitherto unappreciated role for changes in the protein phosphorylation landscape in cellular responses to IFN-I and thus provide insights for novel diagnostic and therapeutic strategies for neurological diseases caused by IFN-I.
Indexed as
Identifiers
What Socratic 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 Socratic graph.