MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer&amp;rsquo;s disease &amp;lt;italic&amp;gt;in vivo&amp;lt;/italic&amp;gt; and&amp;lt;?A3B2 ACK?&amp;gt;&amp;lt;italic&amp;gt;in vitro&amp;lt;/italic&amp;gt;

Ren, Jia-Mou; Zhang, Shuli; Wang, Xiaoling; Deng, Yuxin; Zhao, Yi; Xiao, Yan; Liu, Jian; Chu, Liangzhao; Qi, Xiaolan

doi:10.3724/abbs.2021012

Cited by 14 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The FWER was calculated by multiplying the t -test p -value with the total gene number. Interestingly Mef2c, as a gene known for its high expression in the nervous system, plays a significant role in neuron-development and inflammation regulation ( Ren et al, 2022 ). Recent research has underscored its neuron-protective function in AD ( Ren et al, 2022 ) and identified it as an key player for the epigenetic impact on the neuron-glial cross talk in AD ( Zhou et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly Mef2c, as a gene known for its high expression in the nervous system, plays a significant role in neuron-development and inflammation regulation ( Ren et al, 2022 ). Recent research has underscored its neuron-protective function in AD ( Ren et al, 2022 ) and identified it as an key player for the epigenetic impact on the neuron-glial cross talk in AD ( Zhou et al, 2023 ). Our analysis further suggests that Mef2c in neuron cells might be downregulated through the interaction between Astro-ependymal cells and neuron cells in brain tissue, which shed light on potential mechanisms contributing to the etiology of AD disease.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, a subset of CCIs were consistently detected in the AD samples while being notably absent in the WT samples. Importantly, many of the genes implicated in these CCI interactions were previously linked to AD in the scientific literature ( Ren et al, 2022 ; Zhou et al, 2023 ; Son et al, 2019 ; Carvalho et al, 2023 ; Y; Chen et al, 2022 ; Subhadra, Schaller, and Seeds, 2013 ; Davis et al, 1999 ; Begemann et al, 2010 ; Baubet et al, 2012 ; Cohen et al, 2017 ; Cotrina et al, 2021 ; Zawislak et al, 2017 ). These findings collectively reinforce the credibility of the proposed CCI analysis through RECCIPE, and signify meaningful intercellular communication between various cell types within the context of AD.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

RECCIPE: A new framework assessing localized cell-cell interaction on gene expression in multicellular ST data

Ma,

Song,

Yuan

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Cell-cell interaction (CCI) plays a pivotal role in cellular communication within the tissue microenvironment. The recent development of spatial transcriptomics (ST) technology and associated data analysis methods has empowered researchers to systematically investigate CCI. However, existing methods are tailored to single-cell resolution datasets, whereas the majority of ST platforms lack such resolution. Additionally, the detection of CCI through association screening based on ST data, which has complicated dependence structure, necessitates proper control of false discovery rates due to the multiple hypothesis testing issue in high dimensional spaces. To address these challenges, we introduce RECCIPE, a novel method designed for identifying cell signaling interactions across multiple cell types in spatial transcriptomic data. RECCIPE integrates gene expression data, spatial information and cell type composition in a multivariate regression framework, enabling genome-wide screening for changes in gene expression levels attributed to CCIs. We show that RECCIPE not only achieves high accuracy in simulated datasets but also provides new biological insights from real data obtained from a mouse model of Alzheimer’s disease (AD). Overall, our framework provides a useful tool for studying impact of cell-cell interactions on gene expression in multicellular systems.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

RECCIPE: A new framework assessing localized cell-cell interaction on gene expression in multicellular ST data

Ma,

Song,

Yuan

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…MEF2C is considered a transcription activator that binds to the genome and is widely involved in biological processes such as apoptosis, differentiation and neurogenesis (Adriao et al, 2022; de Araujo Tavares et al, 2023; Mohajeri et al, 2022; Ren et al, 2022). MEF2C also plays an important role in controlling the development of cortical synaptic connectivity, elimination and plasticity (Assali et al, 2019; Harrington et al, 2016; Zang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

MEF2C contributes to axonal branching by regulating Kif2c transcription

Wu,

Sun,

Zhou

et al. 2024

Eur J of Neuroscience

View full text Add to dashboard Cite

Neurons are post‐mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin‐13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.

show abstract

“…Aluminum chloride (Castorina et al, 2010) BACE2 cDNA-containing plasmid transfection (Sun et al, 2005) Docosahexaenoic acid (Bie et al, 2021) Lentivirus-mediated overexpression (Sun et al, 2005;Wang et al, 2020) Leptin (Niedowicz et al, 2013) Lethal-7c (let-7c) microRNA transfection (Liu et al, 2022) Lysine acetyltransferase 8 (KAT8) transfection (Chen et al, 2020) Lysosomal inhibition (Liu et al, 2013) Morphine and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) (Pak et al, 2005) Nsmce1 (murine homolog of NSE1) knockdown (Gong et al, 2020) Oxidative stress (H 2 O 2 ) (Azmi et al, 2015) Regulator of calcineurin 1 (RCAN1, inhibitor of proteasomal degradation) (Qiu et al, 2020) Thy1-BACE2 expression cassette microinjection (Azkona, Amador-Arjona, et al, 2010) Decreasing of BACE2 expression APP-binding benzofuran compounds (Espeseth et al, 2005) BACE2 gene knockout (Dominguez et al, 2005;Sun et al, 2005) CRISPR/Cas9-mediated elimination of BACE2 gene (Alić et al, 2021) Mulberry extracts (Song et al, 2014) Myocyte enhancer factor 2C (MEF2C) knockdown (Ren et al, 2022) Nsmce1 overexpression (Gong et al, 2020) RNA silencing (via small interfering RNA [siRNA]) of the α7 nicotinic acetylcholine receptor (Qi et al, 2013) Transfection of siRNA targeting BACE2 (Basi et al, 2003;Casas et al, 2010;Rochin et al, 2013;Wang et al, 2020) Note: BACE2 cleaves amyloid precursor protein (APP) in a nonamyloidogenic manner, but may also cleave APP at its β-secretase site, promoting the production of Aβ. Because of uncertainty about the role of BACE2 in AD pathogenesis, both overexpression and reduced expression of BACE2 have been accomplished by various approaches in experimental systems.…”

Section: Increasing Of Bace2 Expressionmentioning

confidence: 99%

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Loeffler

2023

Journal of Neurochemistry

View full text Add to dashboard Cite

Cerebral clearance of amyloid β‐protein (Aβ) is decreased in early‐onset and late‐onset Alzheimer's disease (AD). Aβ is cleared from the brain by enzymatic degradation and by transport out of the brain. More than 20 Aβ‐degrading enzymes have been described. Increasing the degradation of Aβ offers an opportunity to decrease brain Aβ levels in AD patients. This review discusses the direct and indirect approaches which have been used in experimental systems to alter the expression and/or activity of Aβ‐degrading enzymes. Also discussed are the enzymes' regulatory mechanisms, the conformations of Aβ they degrade, where in the scheme of Aβ production, extracellular release, cellular uptake, and intracellular degradation they exert their activities, and changes in their expression and/or activity in AD and its animal models. Most of the experimental approaches require further confirmation. Based upon each enzyme's effects on Aβ (some of the enzymes also possess β‐secretase activity and may therefore promote Aβ production), its direction of change in AD and/or its animal models, and the Aβ conformation(s) it degrades, investigating the effects of increasing the expression of neprilysin in AD patients would be of particular interest. Increasing the expression of insulin‐degrading enzyme, endothelin‐converting enzyme‐1, endothelin‐converting enzyme‐2, tissue plasminogen activator, angiotensin‐converting enzyme, and presequence peptidase would also be of interest. Increasing matrix metalloproteinase‐2, matrix metalloproteinase‐9, cathepsin‐B, and cathepsin‐D expression would be problematic because of possible damage by the metalloproteinases to the blood brain barrier and the cathepsins' β‐secretase activity. Many interventions which increase the enzymatic degradation of Aβ have been shown to decrease AD‐type pathology in experimental models. If a safe approach can be found to increase the expression or activity of selected Aβ‐degrading enzymes in human subjects, then the possibility that this approach could slow the AD progression should be examined in clinical trials.

show abstract

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

Cited by 14 publications

References 46 publications

RECCIPE: A new framework assessing localized cell-cell interaction on gene expression in multicellular ST data

RECCIPE: A new framework assessing localized cell-cell interaction on gene expression in multicellular ST data

MEF2C contributes to axonal branching by regulating Kif2c transcription

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Contact Info

Product

Resources

About