ArticleFrontiers in cellular neuroscience2015
Role of TGFβ signaling in the pathogenesis of Alzheimer's disease.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Osteopontin in Alzheimer's Disease: A Double-Edged Sword in Neurodegeneration and Neuroprotection-A Systematic Review.CNS neuroscience & therapeutics · 2025Pooled it
- Mediterranean Diet Modulation of Neuroinflammation-Related Genes in Elderly Adults at High Cardiovascular Risk.Nutrients · 2024Trial
- Genetic and pathway complexity in Alzheimer's disease: Insights from multi-omic data about the immune response and mitochondrial function.Neural regeneration research · 2026Article
- Cerebrospinal Fluid Transforming Growth Factor β Isoforms and Disease Progression in Alzheimer's Disease: Longitudinal Evidence from the ADNI Cohort.Neurology international · 2026Article
- Primary cilia-extracellular vesicle crosstalk in Alzheimer's disease: Emerging mechanisms and biomarker potential.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Post-translational modifications in the brain are critical contributors to Alzheimer's disease neuropathology and cognitive decline.bioRxiv : the preprint server for biology · 2026Article
- Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.Journal of translational medicine · 2026Article
- Impaired TGFβ Signaling in Plaque-Associated Microglia.Biomolecules · 2026Article
- Age-Related Changes in Neuron-Microglia Interaction Mediated by Fractalkine Under Inflammatory Conditions.International journal of molecular sciences · 2025Article
- Article
- Uncovering the Associations of LILRB4 Genotypes With Parkinson's Disease: From Clinical Traits to Potential Pathologies.CNS neuroscience & therapeutics · 2025Article
- Mechanotransduction for therapeutic approaches: Cellular aging and rejuvenation.APL bioengineering · 2025Review
- Inflammatory Bridges: Interconnections Between Alzheimer's Disease and Bone Health.Aging and disease · 2025Review
- Acute Communication Between Microglia and Nonparenchymal Immune Cells in the Anti-Aβ Antibody-Injected Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Low-Dose Paracetamol Treatment Protects Neuronal Oxidative Stress and Neuroinflammation in D-Galactose-Induced Accelerated Aging Model.Scientifica · 2025Article
- Implications of Krüppel-like factor signaling in neuroinflammation for neurodegenerative diseases.American journal of translational research · 2025Review
- Oxidative Stress and the Role of Immune Cells in Alzheimer's Disease: Therapeutic Implications and Future Perspectives.CNS & neurological disorders drug targets · 2025Review
- GeneCOCOA: Detecting context-specific functions of individual genes using co-expression data.PLoS computational biology · 2025Article
- Integrated genomic analysis and CRISPRi implicatesNPJ dementia · 2025Article
- Pathogenesis and therapeutic applications of microglia receptors in Alzheimer's disease.Frontiers in immunology · 2025Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is the main risk factor for Alzheimer's disease (AD); being associated with conspicuous changes on microglia activation. Aged microglia exhibit an increased expression of cytokines, exacerbated reactivity to various stimuli, oxidative stress, and reduced phagocytosis of β-amyloid (Aβ). Whereas normal inflammation is protective, it becomes dysregulated in the presence of a persistent stimulus, or in the context of an inflammatory environment, as observed in aging. Thus, neuroinflammation can be a self-perpetuating deleterious response, becoming a source of additional injury to host cells in neurodegenerative diseases. In aged individuals, although transforming growth factor β (TGFβ) is upregulated, its canonical Smad3 signaling is greatly reduced and neuroinflammation persists. This age-related Smad3 impairment reduces protective activation while facilitating cytotoxic activation of microglia through several cellular mechanisms, potentiating microglia-mediated neurodegeneration. Here, we critically discuss the role of TGFβ-Smad signaling on the cytotoxic activation of microglia and its relevance in the pathogenesis of AD. Other protective functions, such as phagocytosis, although observed in aged animals, are not further induced by inflammatory stimuli and TGFβ1. Analysis in silico revealed that increased expression of receptor scavenger receptor (SR)-A, involved in Aβ uptake and cell activation, by microglia exposed to TGFβ, through a Smad3-dependent mechanism could be mediated by transcriptional co-factors Smad2/3 over the MSR1 gene. We discuss that changes of TGFβ-mediated regulation could at least partially mediate age-associated microglia changes, and, together with other changes on inflammatory response, could result in the reduction of protective activation and the potentiation of cytotoxicity of microglia, resulting in the promotion of neurodegenerative diseases.
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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.