ArticleJournal of neuroinflammation2021
Thymosin β4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PS1 mice.
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 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Histological Insights into the Neuroprotective Effects of Antioxidant Peptides and Small Molecules in Cerebral Ischemia.Molecules (Basel, Switzerland) · 2025Pooled it
- Thymosin β4 Mitigates Acute Cerebral Infarction Via Inhibition of the TLR4/NF-κB Pathway and Suppression of Neuronal Pyroptosis.Applied biochemistry and biotechnology · 2026Article
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Zinc Coordination by Thymosin β4: Structural Determinants and Functional Implications.International journal of molecular sciences · 2026Article
- Human iPSC-Derived Mononuclear Phagocytes Improve Cognition and Neural Health across Multiple Mouse Models of Aging and Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.Stem cell reports · 2025Article
- Tβ4-exosome-loaded hemostatic and antibacterial hydrogel to improve vascular regeneration and modulate macrophage polarization for diabetic wound treatment.Materials today. Bio · 2025Article
- Study of Intracellular Peptides of the Central Nervous System of Zebrafish (International journal of molecular sciences · 2025Article
- Thymosin β4 Regulates Tissue Inflammatory Response in Mouse Nonalcoholic Fatty Liver Disease by Promoting Macrophage M2-Type Polarization.Journal of inflammation research · 2025Article
- Negative symptoms and neurocognition in drug-naïve schizophrenia: moderating role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and interferon-gamma (INF-γ).European archives of psychiatry and clinical neuroscience · 2024Article
- Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease.Brain : a journal of neurology · 2023Article
- Network pharmacology andHeliyon · 2023Article
- Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer's disease and brain aging.Journal of neuroinflammation · 2023Article
- The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats.Reproductive biology and endocrinology : RB&E · 2022Article
- Microglia Polarization From M1 to M2 in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Gut microbiota may be involved in Alzheimer's disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice.Frontiers in aging neuroscience · 2022Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer's disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
methodsBehavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice.
resultsWe demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects.
conclusionsThese results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.
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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.