The molecular mechanism of γ-aminobutyric acid against AD: the role of CEBPα/circAPLP2/miR-671-5p in regulating CNTN1/2 expression

Liu, An; Meng, Na; Pan, Pengyu; Hu, Shuang; Miao, Chen; Hu, Yixin; Wang, Fangfang; Zhang, Jingzhu

doi:10.1039/d2fo03049g

Cited by 2 publications

(1 citation statement)

References 40 publications

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“…3B), which are listed in Table SIII. Of these miRNAs (labeled with # in Table SIII) 13 are upregulated in animal models of AD or cognitive deficits (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Furthermore, an analytical targeting analysis of the remaining miRNAs was performed using the miRanda database.…”

Section: Tri Inhibits Lps-mediated Upregulation Of Neat1 Expressionmentioning

confidence: 99%

Triptolide improves Alzheimer's disease by regulating the NF‑κB signaling pathway through the lncRNA NEAT1/microRNA 361‑3p/TRAF2 axis

Zhou,

Huang,

et al. 2023

Exp Ther Med

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Alzheimer's disease (AD) is the most common type of dementia and is a serious social and medical problem threatening human health. The present study investigated the effect and underlying action mechanism of triptolide (Tri) on AD progression. Reverse transcription-quantitative PCR and western blotting analysis were used to determine the changes in RNA expression and levels of NF-κB signaling pathway proteins before and after lipopolysaccharide (LPS) induction. Nucleocytoplasmic separation experiments determined the intracellular localization of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1). A dual-luciferase assay was used to analyze the binding between NEAT1 and microRNA (miRNA/miR)-361 or tumor necrosis factor receptor-associated factor 2 (TRAF2) and miR-361-3p and RNA pull-down was used to analyze the binding between NEAT1 and miR-361-3p. Cell Counting Kit-8, flow cytometry and ELISA were used to detect the effects of interaction between Tri and NEAT1/miR-361-3p/TRAF2 on cell viability, apoptosis and inflammatory factor levels, respectively. The results showed that LPS-mediated human microglial clone 3 cell line (HMC3) viability decreased and apoptosis and inflammatory factors (IL-1β, IL-6, IL-18 and TNF-α) increased. Tri inhibited LPS-mediated effects in a dose-dependent manner by downregulating NEAT1 expression. NEAT1 is highly expressed in the cytoplasm and reduces the transcription and translation of downstream TRAF2 by acting as a competitive endogenous RNA that adsorbs miR-361-3p. LPS-mediated HMC3 cell injury, inflammation and activation of NF-κB signaling were partially reversed in presence of Tri. The miR-361-3p mimic promoted the Tri effect and overexpression of (ov)-NEAT1 partially reversed the Tri-miR-361-3p combined effect. The effects of ov-NEAT1 were partially attenuated by small interfering (si)-TRAF2. Overall, Tri inhibited the LPS-induced decrease in viability, increase in apoptosis and inflammation and activation of NF-κB signaling in HMC3 cells. Tri regulation affected the NEAT1/miR-361-3p/TRAF2 axis. These findings suggested a potential therapeutic role for Tri in the clinical management of AD by modulating this molecular axis.

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Section: Tri Inhibits Lps-mediated Upregulation Of Neat1 Expressionmentioning

confidence: 99%

Triptolide improves Alzheimer's disease by regulating the NF‑κB signaling pathway through the lncRNA NEAT1/microRNA 361‑3p/TRAF2 axis

Zhou,

Huang,

et al. 2023

Exp Ther Med

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Cryo‐EM structures of the full‐length human contactin‐2

Zhang,

Chen,

Shi

et al. 2024

The FEBS Journal

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Contactin‐2 (CNTN2), an immunoglobulin cell adhesion molecule (IgCAM) expressed on the neural cell surface, regulates the formation of myelin sheaths, facilitates communication between neurons and axoglial cells, and coordinates the migration of neural cells. However, the assembly of full‐length CNTN2 is still not fully elucidated. Here, we found that the full‐length human CNTN2 forms a concentration‐dependent homodimer. We further determined the cryo‐EM structures of the full‐length CNTN2, revealing a novel bowknot‐shaped scaffold constituted of the Ig1‐6 repeats from two protomers, with the flexible ribbon‐like FNIII repeats extending outward in opposite directions. The Ig1‐6 domains, rather than the previously proposed Ig1‐4 domains, have an indispensable role in mediating CNTN2‐dependent cell adhesion and clustering. Moreover, structure‐guided mutagenesis analyses supported the idea that CNTN2 homodimerization observed in our structure is essential for cell adhesion. Our findings offer novel insights into the mechanism through which CNTN2 forms a homodimer to maintain cell–cell contacts in the nervous system.

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The molecular mechanism of γ-aminobutyric acid against AD: the role of CEBPα/circAPLP2/miR-671-5p in regulating CNTN1/2 expression

Abstract: The extracellular accumulation of amyloid- peptide (Aβ) in neuritic plaques is a classic pathological feature of Alzheimer’s disease (AD), and synaptic structure and function abnormalities closely relate to cognitive impairment....

Cited by 2 publications

References 40 publications

Triptolide improves Alzheimer's disease by regulating the NF‑κB signaling pathway through the lncRNA NEAT1/microRNA 361‑3p/TRAF2 axis

Triptolide improves Alzheimer's disease by regulating the NF‑κB signaling pathway through the lncRNA NEAT1/microRNA 361‑3p/TRAF2 axis

Cryo‐EM structures of the full‐length human contactin‐2

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