CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

Jiang, Hui; Niu, Fengnan; Zheng, Yan; Xu, Yun

doi:10.3892/mmr.2021.11919

Cited by 17 publications

(10 citation statements)

References 41 publications

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“…Additionally, we found that miR-668-3p was upregulated in the GEO data analysis, AD mouse models, and in vitro Aβ1-42-induced NSCs. These results were consistent with those of previous studies ( 51 - 53 ), and we found that in vitro Aβ1-42 induction decreased NSC proliferation and promoted apoptosis, cell cycle arrest, and oxidative stress. By suppressing miR-668-3p expression, the adverse effects of Aβ1-42 induction on cells could be reversed.…”

Section: Discussionsupporting

confidence: 94%

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

Li¹,

Wu²,

Ma³

et al. 2022

Ann Transl Med

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Background Alzheimer’s disease (AD) is the most common type of dementia in old age and has become a serious social and medical problem threatening human health. We aimed to explore the mechanisms underlying AD development by screening for microRNAs (miRNAs) that affect AD progression and examining their role in AD development. Methods Hematoxylin-eosin (HE) staining, immunohistochemistry, and immunofluorescence (IF) were used to analyze the characteristics of the hippocampus, neuron cell separation, and related protein expression in mice. We used Gene Expression Omnibus (GEO) data analysis to screen miRNAs and mRNAs that affect AD progression, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis to determine changes in miRNA and mRNA levels before and after amyloid β (Aβ)1-42 induction. In addition, we used luciferase analysis to examine miRNA and mRNA binding and the effect of miRNA/mRNA interaction on neuronal cell proliferation. Apoptosis and reactive oxygen species (ROS) levels were examined using Cell Counting Kit-8 analysis and flow cytometry (FCM), respectively. The enzyme-linked immunosorbent assay was used to analyze changes in neuronal cell-secreted oxidative stress-related protein levels through miRNA/mRNA interaction. Results Oxidative stress levels were significantly increased in the AD mouse model. GEO data analysis revealed 67 dysregulated miRNAs, and miR-668-3p was identified as a potential therapeutic target for AD. We found that the AD and Aβ1-42-induced models showed an increase in miR-668-3p and a decrease in oxidation resistance 1 ( OXR1 ) expression. The luciferase analysis results revealed that miR-668-3p may play a role in AD development by targeting OXR1 and promoting intracellular oxidative stress by activating p53-p21 signaling. The final rescue experiment also confirmed that Aβ1-42-induction decreased cell proliferation, increased apoptosis, increased cell cycle arrest, and promoted oxidative stress. Tenovin-1 (TEN) enhanced the effect of Aβ1-42, and the miR-668-3p inhibitor partially alleviated it, although the effect of the miR-668-3p inhibitor was weakened by TEN. Conclusions MiR-668-3p negatively regulated OXR1 expression by targeting OXR1 , affecting p53-p21 protein signaling, and regulating cell damage and oxidative stress induced by Aβ1-42. Therefore, miR-668-3p may be a potential therapeutic target for AD.

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Section: Discussionsupporting

confidence: 94%

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

Li¹,

Wu²,

Ma³

et al. 2022

Ann Transl Med

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“…Moreover, the level of 8-hydroxydeoxyguanosine (8-OHdG), a widely used DNA oxidative marker, was a threefold increase in the postmortem brain tissue of AD patients compared with age-matched controls [ 139 ]. Similar results were found in AD-like animal models [ 44 , 140 ]. Furthermore, the oxidative damage of protein induced by excessive free radicals was detected in sporadic AD rat and transgenic AD models [ 7 , 44 , 141 ].…”

Section: Introductionsupporting

confidence: 87%

Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges

Yang

Feng

et al. 2022

Inflamm Regener

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Alzheimer’s disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients’ and families’ quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.

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“… Jin et al (2015) found that exogenous CART administration improved memory impairment in AD mice. In addition, CART could promote Aβ degradation by regulating Aβ metabolism-associated enzymes ( Jiang et al, 2021 ). Hence, in this study, all 35 AD-related targets, including CARTPT, were considered hub targets for further analysis.…”

Section: Discussionmentioning

confidence: 99%

HIF-1 signalling pathway was identified as a potential new pathway for Icariin’s treatment against Alzheimer’s disease based on preclinical evidence and bioinformatics

You

Yuan

et al. 2022

Front. Pharmacol.

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Aim: Alzheimer’s disease (AD) is a neurodegenerative condition that is characterized by the gradual loss of memory and cognitive function. Icariin, which is a natural chemical isolated from Epimedii herba, has been shown to protect against AD. This research examined the potential mechanisms of Icariin’s treatment against AD via a comprehensive review of relevant preclinical studies coupled with network pharmacology.Methods: The PubMed, Web of Science, CNKI, WANFANG, and VIP databases were used to identify the relevant studies. The pharmacological characteristics of Icariin were determined using the SwissADME and TCMSP databases. The overlapping targets of Icariin and AD were then utilized to conduct disease oncology (DO) analysis to identify possible hub targets of Icariin in the treatment of AD. The hub targets were then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the interactions of the targets and Icariin were assessed via molecular docking and molecular dynamics simulation (MDS).Results: According to the literature review, Icariin alleviates cognitive impairment by regulating the expression of Aβ1-42, Aβ1-40, BACE1, tau, hyperphosphorylated tau, and inflammatory mediators. DO analysis revealed 35 AD-related hub targets, and the HIF-1 signalling pathway was ranked first according to the KEGG pathway analysis. Icariin effectively docked with the 35 hub targets and HIF-1α, and the dynamic binding of the HIF-1-Icariin complex within 100 ns indicated that Icariin contributed to the stability of HIF-1α.Conclusion: In conclusion, our research used a literature review and network pharmacology methods to identify the HIF-1 signalling pathway as a potential pathway for Icariin’s treatment against AD.

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CART mitigates oxidative stress and DNA damage in memory deficits of APP/PS1 mice via upregulating β‑amyloid metabolism‑associated enzymes

Cited by 17 publications

References 41 publications

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges

HIF-1 signalling pathway was identified as a potential new pathway for Icariin’s treatment against Alzheimer’s disease based on preclinical evidence and bioinformatics

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