The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway

Fang, Yinquan; Wang, Jianbo; Yao, Lemeng; Li, Chenhui; Wang, Jing; Liu, Yuan; Xia, Tao; Sun, Hao; Liao, Hong

doi:10.1186/s12974-018-1250-1

Cited by 30 publications

(21 citation statements)

References 67 publications

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“…Nogo-A is the longest isomer, enriched in CNS, while NgR is the receptor of Nogo (7). Nogo/NgR signaling pathway has been reported to be related to brain injury, and the inhibition of its activation can reduce the death of microglial cells (8). Effect of miR-124 on the proliferation and differentiation of U87 glioma stem cells and its effect on Nogo/NgR signaling pathway were analyzed in this study to explore its mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

miR‑124 participates in the proliferation and differentiation of brain glioma stem cells through regulating Nogo/NgR expression

2019

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The effect of miR-124 on the proliferation and differentiation of brain glioma stem cells and Nogo/NgR signaling pathway were investigated. miR-124 mimic, miR-124 inhibitor and miR-control expression vector were designed and produced to transfect U87 glioma stem cells. The results of transfection were tested via RT-qPCR and the expression of protein was detected by western blot analysis. Cell proliferation was detected by MTT proliferation and the proportion of CD133+ cells was detected by immunomagnetic beads to determine cell differentiation. The correlation between miR-124 and Nogo-A, and NgR protein expression was analyzed by Spearman correlation analysis. The relative expression of miR-124 in cells of miR-124 mimic group was significantly higher than that of miR-124 inhibitor and miR-control groups (P<0.05). The relative expression of Nogo-A and NgR protein in cells of the miR-124 mimic group was significantly lower than that of miR-124 inhibitor and miR-control groups (P<0.05). Absorbance values of the cells in the miR-124 mimic and miR-control groups were significantly lower than those in the miR-124 inhibitor group at each time point (P<0.05), while the values of the cells in the miR-124 mimic group were significantly lower than that in miR-control group (P<0.05). The level of CD133+ cells in miR-124 mimic group was significantly lower than that in miR-124 inhibitor and miR-control groups (P<0.05), while the level of CD133+ cells in miR-124 inhibitor group was higher than that in miR-control group (P<0.05). Correlation analysis revealed that there was a negative correlation between miR-124 and the expression of Nogo-A and NgR protein (P<0.05). miR-124 may participate in the differentiation of brain glioma stem cells through the Nogo/NgR pathway, which may bring a new direction for the clinical treatment of brain glioma.

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Section: Introductionmentioning

confidence: 99%

miR‑124 participates in the proliferation and differentiation of brain glioma stem cells through regulating Nogo/NgR expression

2019

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“…Overactivation of microglia is closely related to the progression of Alzheimer's disease, and microglial migration plays an important role in the activation of microglia. In Alzheimer's disease, microglial migration towards soluble A β is an important process of phagocytosis [ 14 ]. Furthermore, microglia migrate to senile plaques constituting a barrier which prevents outward plaque expansion and limits inward accumulation of protofibrillar A β aggregates [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN)

Lin

et al. 2020

Neural Plasticity

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Microglia activation contributes to Alzheimer’s disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN.

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“…Chemokines are crucial factors for an early in ammatory response that evoke migration of the microglial cells [32]. Microglial cells migrate to the site of injury or lesion, and play a pivotal role in the occurrence, and development of in ammation [33]. In this study, immuno uorescence of Iba-1, wound healing assay and transwell migration assay were performed to test whether artemisinin could reduce the migratory capacity of microglia cells.…”

Section: Discussionmentioning

confidence: 99%

Artemisinin protects against sepsis-associated encephalopathy by activating the AMPK axis in the microglia

Shen¹,

Jiang²,

S³

et al. 2019

Preprint

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Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in sepsis-associated encephalopathy (SAE) remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of action of artemisinin on SAE. Methods: Male C57BL/6mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of SAE. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical analysis. Additionally, the protective mechanism of artemisinin was determined in vitro. Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. Luminex liquid chip revealed that artemisinin could inhibit the pro-inflammatory cytokines and chemokines induced by LPS in the BV2 microglia cells. Meanwhile, artemisinin suppressed the migratory ability of BV2 cells. Western blot demonstrated that artemisinin promoted adenosine monophosphate-activated protein kinaseα1 (AMPKα1) expression and suppressed nuclear translocation of NF-κB. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin when exposed to LPS. Conclusion: Artemisinin is a potential therapeutic agent for SAE, and its effect was probably mediated by the activation of AMPKα1signalling pathway in microglia.

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The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway

Cited by 30 publications

References 67 publications

miR‑124 participates in the proliferation and differentiation of brain glioma stem cells through regulating Nogo/NgR expression

miR‑124 participates in the proliferation and differentiation of brain glioma stem cells through regulating Nogo/NgR expression

Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN)

Artemisinin protects against sepsis-associated encephalopathy by activating the AMPK axis in the microglia

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