ArticleNeurobiology of disease2021
Type I interferon response-related microglial Mef2c deregulation at the onset of Alzheimer's pathology in 5×FAD mice.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Review
- MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer's disease risk in macrophages.Research square · 2026Article
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease.Nature immunology · 2025Article
- KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Co-regulation of microglial subgroups in Alzheimer's amyloid pathology: Implications for diagnosis and drug development.PloS one · 2025Article
- Brain derived β-interferon is a potential player in Alzheimer's disease pathogenesis and cognitive impairment.Alzheimer's research & therapy · 2024Article
- Mef2c Exacerbates Neuron Necroptosis via Modulating Alternative Splicing of Cflar in Ischemic Stroke With Hyperlipidemia.CNS neuroscience & therapeutics · 2024Article
- Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders.Journal of leukocyte biology · 2024Review
- Analysis ofBiomedicines · 2024Article
- METTL3 promotes microglial inflammation via MEF2C in spinal cord injury.Cell and tissue research · 2024Article
- In sickness and in health-Type I interferon and the brain.Frontiers in aging neuroscience · 2024Review
- Alzheimer's genes in microglia: a risk worth investigating.Molecular neurodegeneration · 2023Review
- Article
- MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience.Nature neuroscience · 2023Article
- Article
- Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder with multifactorial etiology. The role of microglia in the pathogenesis of AD has been increasingly recognized in recent years; however, the detailed mechanisms shaping microglial phenotypes in AD-relevant pathological settings remain largely unresolved. Myocyte-specific enhancer factor 2C (Mef2C) is a transcription factor with versatile functions. Recent studies have attributed aging-related microglial changes to type I interferon (IFN-I)-associated Mef2C deregulation. In view of the close relationship between brain aging and AD, it is of great interest to determine microglial Mef2C changes in AD-related conditions. In this study, we have found that suppressed Mef2C nuclear translocation was an early and prominent microglial phenotype in a mouse model of brain amyloidosis (5×FAD mice), which exacerbated with age. Echoing the early Mef2C deregulation and its association with microglial activation, transcriptional data showed elicited IFN-I response in microglia from young 5×FAD mice. Amyloid beta 42 (Aβ42) in its oligomeric forms promoted Mef2C deregulation in microglia on acute organotypic brain slices with augmented microglial activation and synapse elimination via microglial phagocytosis. Importantly, these oligomeric Aβ42-mediated microglial changes were substantially attenuated by blocking IFN-I signaling. The simplest interpretation of the results is that Mef2C, concurring with activated IFN-I signaling, constitutes early microglial changes in AD-related conditions. In addition to the potential contribution of Mef2C deregulation to the development of microglial phenotypes in AD, Mef2C suppression in microglia may serve as a potential mechanistic pathway linking brain aging and AD.
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Registered trials
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