Inhibition of miR-129 Improves Neuronal Pyroptosis and Cognitive Impairment Through IGF-1/GSK3β Signaling Pathway: An In Vitro and In Vivo Study

Wang, Feng; Wang, Lu; Sui, Guanghong; Yang, Caixia; Guo, Mengtian; Xiong, Xiangyang; Chen, Zheng; Zhang, Qiang; Lei, Ping

doi:10.1007/s12031-021-01794-x

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Overexpression of miR-9.T and miR-129-2-3p.T throughout the brain using AAV-PHP.B. Cellular microRNAs, including miR-9 and miR-129-2-3p, play critical roles in cellular functions such as cell survival, dendritic branching, and synaptic plasticity [45][46][47][48][49] . Entrapment of endogenous miRNAs by overexpressed miR.T sequences in neurons and/or other cell types may impair the inherent roles of miRNAs and consequently disrupt cellular functions.…”

Section: Resultsmentioning

confidence: 99%

Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo

et al. 2022

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Here we describe the microglia-targeting adeno-associated viral (AAV) vectors containing a 1.7-kb putative promoter region of microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (Iba1), along with repeated miRNA target sites for microRNA (miR)-9 and miR-129-2-3p. The 1.7-kb genomic sequence upstream of the start codon in exon 1 of the Iba1 (Aif1) gene, functions as microglia preferential promoter in the striatum and cerebellum. Furthermore, ectopic transgene expression in non-microglial cells is markedly suppressed upon adding two sets of 4-repeated miRNA target sites for miR-9 and miR-129-2-3p, which are expressed exclusively in non-microglial cells and sponged AAV-derived mRNAs. Our vectors transduced ramified microglia in healthy tissues and reactive microglia in lipopolysaccharide-treated mice and a mouse model of neurodegenerative disease. Moreover, live fluorescent imaging allowed the monitoring of microglial motility and intracellular Ca2+ mobilization. Thus, microglia-targeting AAV vectors are valuable for studying microglial pathophysiology and therapies, particularly in the striatum and cerebellum.

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Section: Resultsmentioning

confidence: 99%

Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo

et al. 2022

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“…Among them, the insulin-like growth factor (IGF) plays an important regulatory role in CRC and other malignant tumors, indicating that circRUNX1 can be used as a tumor promoter and is expected to become a potential drug treatment target for CRC. [105][106][107][108][109] In CRC, circPVT1 is upregulated and participates in the proliferation and metastasis of CRC. However, it is noteworthy that overexpression of miR-145 significantly reverses the effect of upregulated circPVT1 on the metastasis of CRC, suggesting that miR-145 is a key downstream effector of circPVT1-mediated CRC metastasis.…”

Section: Cytoplasmmentioning

confidence: 99%

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

Zhang

Sun

et al. 2021

Cancer Medicine

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Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, and morbidity and mortality rank third and second in malignant tumors. [1][2][3] Currently, early screening for CRC can effectively improve the survival rate of patients with CRC, but approximately 25% of CRC patients develop metastatic disease from an early stage. [4][5][6] Therefore, a promising field of antimetastatic therapy lies in the targeted inhibition of cancer cells with high metastatic potential from the primary site. 7,8 Recently, there has been a qualitative leap in tumor medical technology, such as the application of laparoscopic surgery, nano-assembly technology, PET/ CT imaging technology, and dynamic network biomarker (DNB), etc. 9-11 However, the cure rate and survival rate of CRC are still very low, mainly lacking new drug treatment targets and biomarkers for the treatment of CRC. 12 According to the research of circular RNAs in the CRC field, circular RNAs are expected to be therapeutic targets

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“…We will explore whether the inhibitory effect of MSCs on ferroptosis after rmTBI will affect other neuropathology using GPx4 knockout mice (ferroptosis over-activated) in future studies. However, while ferroptosis emerges as a critical cell death form in rmTBI, other programmed cell death pathways, including apoptosis, pyroptosis, necroptosis, and autophagy will be also activated after brain injury and determine the neuropathology as well as the cognitive prognosis [ 58 – 60 ]. The results of this research suggested that MSCs exert a neuroprotective effect by possibly inhibiting ferroptosis but also possible, by manipulating other cell death pathways.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis

Wang

Zhang

et al. 2022

J Neuroinflammation

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The incidence of repetitive mild traumatic brain injury (rmTBI), one of the main risk factors for predicting neurodegenerative disorders, is increasing; however, its underlying mechanism remains unclear. As suggested by several studies, ferroptosis is possibly related to TBI pathophysiology, but its effect on rmTBI is rarely studied. Mesenchymal stromal cells (MSCs), the most studied experimental cells in stem cell therapy, exert many beneficial effects on diseases of the central nervous system, yet evidence regarding the role of MSCs in ferroptosis and post-rmTBI neurodegeneration is unavailable. Our study showed that rmTBI resulted in time-dependent alterations in ferroptosis-related biomarker levels, such as abnormal iron metabolism, glutathione peroxidase (GPx) inactivation, decrease in GPx4 levels, and increase in lipid peroxidation. Furthermore, MSC treatment markedly decreased the aforementioned rmTBI-mediated alterations, neuronal damage, pathological protein deposition, and improved cognitive function compared with vehicle control. Similarly, liproxstatin-1, a ferroptosis inhibitor, showed similar effects. Collectively, based on the above observations, MSCs ameliorate cognitive impairment following rmTBI, partially via suppressing ferroptosis, which could be a therapeutic target for rmTBI.

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Inhibition of miR-129 Improves Neuronal Pyroptosis and Cognitive Impairment Through IGF-1/GSK3β Signaling Pathway: An In Vitro and In Vivo Study

Cited by 10 publications

References 24 publications

Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo

Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis

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