Inhibition of <scp>ANXA2</scp> activity attenuates epileptic susceptibility and <scp>GluA1</scp> phosphorylation

Ma, Limin; Wu, Qingyuan; Yuan, Jinxian; Wang, You; Zhang, Peng; Liu, Qiankun; Tan, Dandan; Liang, Minxue; Chen, Yangmei

doi:10.1111/cns.14295

Cited by 4 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After tail vein injection of neuronal EVs for 48 h, 20 mM kainic acid (KA) (50 nL, Sigma-Aldrich) was injected into the CA1 region of the unilateral hippocampus to establish an epilepsy mouse model Ma et al, 2023). Mice were placed under a videotracking instrument after KA injection, and spontaneous recurrent seizures (SRSs) were recorded for a period of 28 days.…”

Section: Generation Of a Kainic Acid Epilepsy Model And Behavioral Re...mentioning

confidence: 99%

Neuronal small extracellular vesicles carrying miR‐181c‐5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C‐δ/glutamate transporter‐1 axis in astrocytes

Ma,

Wu,

You

et al. 2024

Glia

Self Cite

View full text Add to dashboard Cite

Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter‐1 (GLT‐1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR‐181c‐5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV‐derived miR‐181c‐5p interacted with protein kinase C‐delta (PKCδ), downregulated PKCδ and GLT‐1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR‐181c‐5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy.

show abstract

Section: Generation Of a Kainic Acid Epilepsy Model And Behavioral Re...mentioning

confidence: 99%

Neuronal small extracellular vesicles carrying miR‐181c‐5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C‐δ/glutamate transporter‐1 axis in astrocytes

Ma,

Wu,

You

et al. 2024

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…ANXA2 has been shown to have a pivotal role in epilepsy. A study demonstrated that ANXA2 plays a significant role in regulating excitatory synaptic activity mediated by the GluA1 subunit of AMPA receptor [37]. Elevated ANXA2 expression was detected in epilepsy patients and models, both in vivo and in vitro.…”

Section: Role Of Annexins In Neurological Disorders Of the Cnsmentioning

confidence: 99%

The role of annexins in central nervous system development and disease

White,

Nair,

Bredel

2024

J Mol Med

View full text Add to dashboard Cite

Annexins, a group of Ca2+-dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+-dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neuronal development, influencing differentiation, proliferation, and synaptic formation in CNS tissues. Notably, annexins such as ANXA1 and ANXA2 play roles in apoptosis and blood-brain barrier (BBB) integrity. Neurological disorders, including Alzheimer’s disease, multiple sclerosis, and depression, involve annexin dysregulation, influencing neuroinflammation, blood-brain barrier integrity, and stress responses. Moreover, annexins contribute to the pathogenesis of CNS tumors, either promoting or suppressing tumor growth, angiogenesis, and invasion. Annexin expression patterns vary across different CNS tumor types, providing potential prognostic markers and therapeutic targets. This review underscores the multifaceted roles of annexins in the CNS, highlighting their importance in normal functioning, disease progression, and potential therapeutic interventions.

show abstract

Identification of candidate biomarkers and signaling pathways associated with Alzheimer’s disease using bioinformatics analysis of next generation sequencing data

Vastrad,

Vastrad

2024

Preprint

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the most common cause of dementia, and one of the most common health problems all over the world. However, the specific molecular mechanisms of AD have not been fully investigated. The current investigation aimed to elucidate potential key candidate genes and signaling pathways in AD. Next generation sequencing (NGS) dataset GSE203206 was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 39 AD samples and 8 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the limma R bioconductor package. These DEGs were subsequently investigated by Gene ontology (GO) and pathway enrichment analysis, and a protein-protein interaction (PPI) network and modules were constructed and analyzed. The miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to identify key miRNAs and TFs. The receiver operating characteristic (ROC) curve analysis was performed to estimate the clinical diagnostic value of the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between AD and normal control samples. GO and pathway enrichment analysis results revealed that the up regulated genes were mainly enriched in response to stimulus, cytoplasm, small molecule binding and signal transduction, whereas down regulated genes were mainly enriched in multicellular organism development, cell junction, ion binding and cardiac conduction. The PPI network contained 4886 nodes and 10342 edges. HSP90AA1, FN1, KIT, YAP1, LSM2, SKP1, EIF5A2, TAF9, DDX39B and CDK7 were identified as the top hub genes. The regulatory network analysis revealed that microRNA (miRNA) hsa-mir-545-3p and hsa-miR-548f-5p, and transcription factor (TF) PLAG1 and MEF2A might be involved in the development of AD. These findings provide new insights into the pathogenesis of AD. The hub genes, miRNAs and TFs have the potential to be used as diagnostic and therapeutic markers.

show abstract

Inhibition of ANXA2 activity attenuates epileptic susceptibility and GluA1 phosphorylation

Cited by 4 publications

References 41 publications

Neuronal small extracellular vesicles carrying miR‐181c‐5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C‐δ/glutamate transporter‐1 axis in astrocytes

Neuronal small extracellular vesicles carrying miR‐181c‐5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C‐δ/glutamate transporter‐1 axis in astrocytes

The role of annexins in central nervous system development and disease

Identification of candidate biomarkers and signaling pathways associated with Alzheimer’s disease using bioinformatics analysis of next generation sequencing data

Contact Info

Product

Resources

About