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Cited by 29Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer’s disease in vivo and<?A3B2 ACK?>in vitro

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Ren, Jiamou, Zhang, Shuli, Wang, Xiaoling, Deng, Yuxin, Zhao, Yi, Xiao, Yan, Liu, Jian, Chu, Liangzhao +1 more·2022·Acta Biochimica et Biophysica Sinica
DOI 10.3724/abbs.2021012PMC PMC9909301
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Abstract

Myocyte enhancer factor 2C (MEF2C) is highly expressed in the nervous system, and regulates neuro-development, synaptic plasticity, and inflammation. However, its mechanism in Alzheimer's disease (AD) is underestimated. In this study, the role and mechanism of MEF2C were investigated in the brain tissue specimens from patients with AD, APPswe/PSEN1dE9 double transgenic (APP/PS1_DT) mice, and SH-SY5Y cells treated with β-amyloid peptide (Aβ). The results indicated that the expression of MEF2C is significantly reduced, and the expression of MEF2C/Aβ in different parts of brain is negatively correlated in patients with AD. Knockdown of MEF2C promotes cell apoptosis and the level of β-amyloid precursor protein cleaving enzyme 1 (BACE) but reduces BACE2 expression. In addition, knockdown of enhances the generation and aggregation of Aβ in the cortex of APP/PS1_DT mice, reduces the expression of synaptic proteins, exacerbates the ability of learning and memory of APP/PS1_DT mice, damages the structure of mitochondria, increases the oxidative stress (OS) level, and inhibits the expression levels of members of the Nrf2-ARE signal pathway. In summary, inhibition of MEF2C exacerbates the toxic effect of Aβ and , damages synaptic plasticity, reduces the ability of learning and memory of APP/PS1 mice, and increases the level of OS via the Nrf2-ARE signal pathway.

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Crossref · 10.3724/abbs.2021012

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  • In APP/PS1 (dE9) mice at 6 and 10 months of age, AAV-induced Mef2c knockdown decreases PSD95 and SYP proteins in the cortex.

    “Amyloid burden↑, apoptosis↑, PSD95 and SYP proteins↓, learning and memory abilities↓”

    From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [48]

    The Results (Figure 9; page unavailable) report reduced cortical PSD95 and SYN in 6- and 10-month-old APP/PS1 mice after Mef2c knockdown. The Methods identify the mice as carrying APPswe/PS1dE9 mutations, but specify adenovirus-delivered shRNA, not AAV. The paper calls the second measured protein SYN rather than SYP. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In APP/PS1 (dE9) mice at 6 and 10 months of age, AAV-induced Mef2c knockdown increases amyloid burden in the cortex.

    “Amyloid burden↑, apoptosis↑, PSD95 and SYP proteins↓, learning and memory abilities↓”

    From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [48]

    The Results section (“Knockdown of Mef2c increased Aβ deposition”) reports increased cortical Aβ aggregation after Mef2c knockdown in APP/PS1 mice; Figure 2 covers mice aged 6 and 10 months. However, Materials and Methods describes delivery by adenovirus (Ad-shRNA-Mef2c), not AAV, so the stated vector is unsupported. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • In APP/PS1 (dE9) mice at 6 and 10 months of age, AAV-induced Mef2c knockdown increases apoptosis in the cortex.

    “Amyloid burden↑, apoptosis↑, PSD95 and SYP proteins↓, learning and memory abilities↓”

    From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [48]

    The Results (Figure 4) report increased cortical apoptosis after Mef2c knockdown in 6- and 10-month-old APP/PS1 mice. However, Materials and Methods describes an adenovirus carrying Ad-shRNA-Mef2c, not an AAV vector; the claimed delivery method is unsupported. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • In APP/PS1 (dE9) mice at 6 and 10 months of age, AAV-induced Mef2c knockdown decreases learning and memory abilities.

    “Amyloid burden↑, apoptosis↑, PSD95 and SYP proteins↓, learning and memory abilities↓”

    From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [48]

    The Results (Figure 3) report reduced learning and memory performance after Mef2c knockdown in 6- and 10-month-old APP/PS1 mice. The Materials and Methods section specifies adenovirus carrying Ad-shRNA-Mef2c, not AAV, so the claimed delivery method is incorrect. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Microglial activation and functional changes in cortical and hippocampal regions during Alzheimer's disease pathology may be ameliorated through transcriptional remodeling within microglia.

    “microglial activation and functional changes, prominently observed in cortical and hippocampal regions during Alzheimer's disease pathology, may be ameliorated through transcriptional remodeling within microglia”

    From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [48]

    The Introduction (page unavailable) says that activating the Nrf2-ARE pathway can reduce inflammatory cytokine release from microglia in an Alzheimer’s mouse model. It does not establish transcriptional remodeling within microglia as the mechanism or locate the claimed microglial changes in both cortical and hippocampal regions. The paper’s Discussion (page unavailable) instead describes its own MEF2C findings in the cortex and neuronal cells. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Authors
Ren, J., Zhang, S., Wang, X., Deng, Y., Zhao, Y., Xiao, Y., Liu, J., Chu, L., & Qi, X.
Affiliations
  • Chinese People's Liberation Army (CN)
  • Guiyang Medical University (CN)
  • Affiliated Hospital of Guizhou Medical University (CN)
Corresponding author
  • Chu, Liangzhao
  • Qi, Xiaolan
ORCID
Venue
Acta Biochimica et Biophysica Sinica
Publisher
China Science Publishing & Media Ltd.
Published
2021-12-28
Volume
54
Issue
1
Pages
77-90
ISSN
1672-9145 (ISSN-L)
DOI
10.3724/abbs.2021012
PMC
PMC9909301
OpenAlex
W4205290174
Cited by
29
References
2
Citations by year
2026: 6 · 2025: 8 · 2024: 9 · 2023: 6
FWCI
2.36
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Acta Biochimica et Biophysica Sinica (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
MEF2C, Alzheimer's disease, amyloid-beta, APP/PS1 double transgenic mice, SH-SY5Y cells, synaptic plasticity, learning and memory, apoptosis, BACE1, BACE2, mitochondrial damage, oxidative stress, Nrf2/ARE pathway, amyloid fibril formation
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Humans, Learning, Memory, Mice, Transgenic, Mitochondria, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Oxidative Stress, Mice, Presenilin-1, MEF2 Transcription Factors

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