Thymosin β4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PS1 mice.

Wang M, Feng LR, Li ZL, Ma KG, Chang KW, Chen XL, Yang PB, Ji SF, Ma YB, Han H, Ruganzua JB, Yang WN, Qian YH

Journal of neuroinflammation28 Jun 2021Cited by 33 (Europe PMC)

PMID34183019PMCIDPMC8240373DOI10.1186/s12974-021-02166-3PepBankPUB-34183019

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone10

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

01AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
Tβ4 protein level was elevated in all APP/PS1 mice; the abstract does not state the comparison.
In plain wordsIn mice with Alzheimer-like disease, Tβ4 protein level was higher in all the mice, with no comparison stated in the abstract.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseTβ4 protein level
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Aging markers · Nervous system and cognition
Source sentences
Summary
We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301901
02AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone led to less brain Aβ accumulation.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 gave less Aβ build-up in the brain.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseBrain Aβ accumulation
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301902
03AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone led to more insulin-degrading enzyme.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 gave more insulin-degrading enzyme.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseInsulin-degrading enzyme (IDE)
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301903
04AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone reversed the phenotypic polarization of microglia and astrocytes to a healthy state.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 moved brain support cells back to a healthy state.
Peptide
Thymosin beta-4 (human)
Outcome
Direction not reportedPhenotypic polarization of microglia and astrocytes
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301904
05AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone improved neuronal function.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 improved nerve cell function.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseNeuronal function
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301905
06AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone improved cognitive behavior performance.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 improved performance in thinking and memory tests.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCognitive behavior performance
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Cognition and memory · Nervous system and cognition
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301906
07AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Tβ4 over-expression alone displayed an antidepressant-like effect.
In plain wordsIn mice with Alzheimer-like disease, extra Tβ4 showed an antidepressant-like effect.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseAntidepressant-like effect
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Anxiety and mood · Mental health and mood
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301907
08AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In APP/PS1 mice, Tβ4 downregulated the TLR4/MyD88/NF-κB p65 inflammatory pathway.
In plain wordsIn mice with Alzheimer-like disease, Tβ4 lowered activity of an inflammatory signaling pathway.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTLR4/MyD88/NF-κB p65 pathway
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Inflammation markers · Nervous system and cognition
Source sentences
Summary
Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301908
09AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In APP/PS1 mice, Tβ4 downregulated the p52-dependent inflammatory pathway.
In plain wordsIn mice with Alzheimer-like disease, Tβ4 lowered activity of a second inflammatory signaling pathway.
Peptide
Thymosin beta-4 (human)
Outcome
Decreasep52-dependent inflammatory pathway
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Inflammation markers · Nervous system and cognition
Source sentences
Summary
Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301909
10AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In APP/PS1 mice, adding the TLR4 antagonist TAK242 or the NF-κB p65 inhibitor PDTC to Tβ4 gave no further effects.
In plain wordsIn mice with Alzheimer-like disease, adding a TLR4 or NF-κB blocker to Tβ4 gave no further effects.
Peptide
Thymosin beta-4 (human)
Outcome
No significant changeAdded effect of TAK242 or PDTC
Study
mousen: not reported in source
APP/PS1 transgenic mice
Outcome group
Inflammation markers · Nervous system and cognition
Source sentences
Summary
While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3418301910

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

Subjects

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