MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

Li, Xin; Zhang, Jiangkuan; Yang, Yuhang; Wu, Qi; Ning, Hanbing

doi:10.1002/cbin.11576

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…Cognitive dysfunction is the main expression of AD. d -galactose- and aluminum chloride-induced dementia model, a reliable animal model that resembles human dementia, has been widely used to screen anti-AD agents. , Aluminum chloride could induce neuronal inflammation and Aβ deposition in mice, resulting in learning and memory impairment. , In this study, we used an AD animal model induced with d -galactose and aluminum chloride to explore the effects of GB on AD. Recent studies have indicated that GB could ameliorate the learning and memory ability of vascular dementia rats .…”

Section: Discussionmentioning

confidence: 99%

“…The animals were randomized into three groups: Con group (control group), AD group (AD model group), and AD + GB group (GB-treated AD). The AD animal model was induced with d -galactose and aluminum chloride, according to previous studies. , Mice in the AD + GB group were intragastrically treated with 0.1% Ginkgolide B (Yuanye Biotechnology Co., Ltd. Shanghai, China) once daily for 2 weeks prior to the induction of AD, then intragastrically treated once daily for 2 weeks after the induction of AD. Mice in the AD and Con groups took the same amount of saline.…”

Section: Methodsmentioning

confidence: 99%

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Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

Liu

Tao

Zhang

et al. 2021

J. Agric. Food Chem.

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Ginkgolide B (GB) is one of the main bioactive components of Ginkgo biloba leaf extracts with neuroprotective activity. However, the neuroprotective mechanism link between the anti-Alzheimer's disease (AD) efficiency of GB and gut microbiota have remained elusive. Here, we elucidated the effect and possible mechanism of GB against cognitive impairment in mice. Male mice were induced with D-galactose and aluminum chloride to establish an AD animal model, and then intragastrically treated with GB. Cognitive function was assessed by an object recognition test and an open-field test. Amyloid deposition and neuropathological change were detected. The levels of receptor for advanced glycation end products (RAGE), Bcl-2, and Bax were detected. Moreover, microbial compositions were measured by 16s rRNA sequencing. Our results showed that GB significantly alleviated cognitive dysfunction, neurodegeneration, and neuropathological changes in AD model mice. Moreover, GB treatment remarkably reduced the levels of RAGE and Bax and increased the level of Bcl-2 in AD model mice. GB treatment reversed the decreased abundance of Lactobacillus and the increased abundance of Bacteroidales, Muribaculaceae, and Alloprevotella, which led to reconstruction of gut microbiota. These findings demonstrated the neuroprotective effects of GB in AD mice, which were partly mediated by modulating gut dysbiosis, indicating that GB might be a potentially active supplement to alleviate AD.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

Liu

Tao

Zhang

et al. 2021

J. Agric. Food Chem.

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“…Several miRNAs have been described as regulators of the expression of factors that influence telomere dynamics [ 14 ]. We observed alterations in the expression of miRNAs previously described, such as regulators of the molecules involved in telomere homeostasis and oxidative stress response [ 46 , 47 , 48 ]. Specifically, we observed an increase in miR-155-5p in ICM patients, whose expression is associated with telomere and genomic instability.…”

Section: Discussionmentioning

confidence: 99%

Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts

et al. 2021

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Although the roles of telomeres and oxidative stress in ischaemic cardiomyopathy (ICM) are known, mechanisms of telomere homeostasis and their relationship with oxidative stress are incompletely understood. We performed two RNA-seq analyses (mRNA n = 23; ncRNA n = 30) and protein validation on left ventricles of explanted hearts from ICM and control subjects. We observed dysregulation of the shelterin and cohesin complexes, which was related to an increase in the response to cellular oxidative stress. Moreover, we found alterations at mRNA level in the mechanisms of telomeric DNA repair. Specifically, increased RAD51D mRNA levels were correlated with left ventricular diameters. RAD51D protein levels were unaltered, however, and were inversely corelated with the miR-103a-3p upregulation. We also observed the overexpression of lncRNAs (TERRA and GUARDIN) involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the TERRA transcription factor ATF7 was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of GUARDIN and its transcription factor FOSL2 were correlated with those of catalase. Therefore, we showed specific alterations in the mechanisms of telomeric DNA repair and protection, and these alterations are related to an increase in the response mechanisms to oxidative stress and cardiac dysfunction in ICM.

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“…The sham group mice received an intraperitoneal injection of PBS. AD model was established according to the previously described protocol 29,30 . In brief, mice were injected intraperitoneally with 150 mg/kg of d ‐galactose and were intragastrically administered 5 mg/kg of AlCl 3 once a day for 40 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

miRNA‐137‐5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin‐specific peptidase 30

Jiang,

Bian,

Chen

et al. 2023

Anim Models and Exp Med

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BackgroundAlzheimer's disease (AD) is a prevalent neurodegenerative disorder causing progressive dementia. Research suggests that microRNAs (miRNAs) could serve as biomarkers and therapeutic targets for AD. Reduced levels of miR‐137 have been observed in the brains of AD patients, but its specific role and downstream mechanisms remain unclear. This study sought to examine the therapeutic potential of miR‐137‐5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms.MethodsThis study utilized bioinformatic analysis and a dual‐luciferase reporter assay to investigate the relationship between miR‐137‐5p and ubiquitin‐specific peptidase 30 (USP30). In vitro experiments were conducted using SH‐SY5Y cells to assess the impact of miR‐137‐5p on Aβ1–42 neurotoxicity. In vivo experiments on AD mice evaluated the effects of miR‐137‐5p on cognition, Aβ1–42 deposition, Tau hyperphosphorylation, and neuronal apoptosis, as well as its influence on USP30 levels.ResultsIt was discovered that miR‐137‐5p mimics efficiently counteract Aβ1–42 neurotoxicity in SH‐SY5Y cells, a protective effect that is negated by USP30 overexpression. In vivo experiments demonstrated that miR‐137‐5p enhances the cognition and mobility of AD mice, significantly reducing Aβ1–42 deposition, Tau hyperphosphorylation, and neuronal apoptosis within the hippocampus and cortex regions. Mechanistically, miR‐137‐5p significantly suppresses USP30 levels in mice, though USP30 overexpression partially buffers against miR‐137‐5p‐induced AD symptom improvement.ConclusionOur study proposes that miR‐137‐5p, by instigating the downregulation of USP30, has the potential to act as a novel and promising therapeutic target for AD.

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MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

Cited by 12 publications

References 32 publications

Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts

miRNA‐137‐5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin‐specific peptidase 30

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