TGF-β Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity
Open accessAbstract
Microglia, the resident immune cells of the central nervous system (CNS), are crucial for normal brain development and function. They become reactive in response to brain injury and disease, a process known as microglial reactivity. This reactivity, along with microglial homeostasis, is tightly regulated by the local microenvironment and interactions with surrounding cells. The TGF-β signaling pathway plays an essential role in this regulation. Recent genetic studies employing microglia-specific manipulation of the TGF-β signaling pathway have shed light on its significance in microglial development, homeostasis and reactivity. This review provides an updated overview of how TGF-β signaling modulates microglial function and reactivity, contributing to our understanding of microglial biology in health and disease.
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Components of the TGF-β signaling axis were represented among the regulated genes in microglia after tau ablation.
“Notably, components of the TGF-β signaling axis were represented among the regulated genes, consistent with partial restoration of homeostatic regulatory pathways [150–152].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [152]
Section 5 (page unavailable) identifies TGF-β pathway components as homeostatic microglial genes, supporting their connection to homeostatic regulation. It does not say those genes were regulated after tau ablation. Section 8 discusses deletion of microglial APOE4 in a tauopathy model, which is a different intervention. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe TGF-β signaling components are consistent with partial restoration of homeostatic regulatory pathways.
“Notably, components of the TGF-β signaling axis were represented among the regulated genes, consistent with partial restoration of homeostatic regulatory pathways [150–152].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [152]
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Alzheimer’s genes in microglia: a risk worth investigating
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The molecular determinants of microglial developmental dynamics
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The relationship between TGF-β1 and cognitive function in the brain
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Depressive symptoms in relation to clinical symptom onset of mild cognitive impairment
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Biallelic mutations in NRROS cause an early onset lethal microgliopathy
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Improving Cognition with Nutraceuticals Targeting TGF-β1 Signaling
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Discovery of novel CSF biomarkers to predict progression in dementia using machine learning
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Microglial Transforming Growth Factor-β Signaling in Alzheimer’s Disease
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Microglia pack a toolbox for life
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“Tgfbr1 is a key component of the “sensome”, the mechanisms microglia utilize to sense and respond to environmental stimuli [60].”
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General Pathophysiology of Microglia
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Advances in proteomic phenotyping of microglia in neurodegeneration
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The proteomic landscape of microglia in health and disease
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Augmentation of transforming growth factor-β signaling for the treatment of neurological disorders
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Self-citationAging Microglia and Their Impact in the Nervous System
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Microglia Colonization Associated with Angiogenesis and Neural Cell Development
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Shea, J. M., & Villeda, S. (2024) · eLife · doi:10.7554/elife.97671.1
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Human Microglial Molecular Alterations in Aging and Alzheimer’s Disease
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- Authors
- Li, L., Sun, B., Harris, O. A., & Luo, J.
- Affiliations
- VA Palo Alto Health Care System (US)
- Corresponding author
- Luo, Jian
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2024-10-28
- Volume
- 12
- Issue
- 11
- Pages
- 2468
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC11592028
- OpenAlex
- W4403809679
- Cited by
- 38
- References
- 109
- Citations by year
- 2026: 25 · 2025: 12 · 2024: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. National Institutes of Health (R01NS092868, RF1AG059694)
- Polytrauma System of Care, VAPAHCS (R01NS092868, RF1AG059694)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- TGF-beta signaling, microglia, microglial activation, microglial homeostasis, microglial development, brain development, central nervous system, microenvironment
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