miR-23b-3p rescues cognition in Alzheimer’s disease by reducing tau phosphorylation and apoptosis via GSK-3β signaling pathways

Jiang, Hailun; Liu, Jianghong; Guo, Shaodong; Zeng, Li; Cai, Zhongdi; Zhang, Junxia; Wang, Linlin; Li, Zhuorong; Liu, Rui

doi:10.1016/j.omtn.2022.04.008

Cited by 32 publications

(16 citation statements)

References 64 publications

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“…The Morris water maze (MWM) test was used to evaluate the impairment of spatial learning and memory of 5 × FAD mice ( Liu et al, 2018 ; Jiang et al, 2022 ; Sun et al, 2022 ). A different cohort from the Cai et al (2022) study was used for MWM test.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

Sun

Zeng

Cai

et al. 2022

Front. Aging Neurosci.

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IntroductionAlzheimer’s disease (AD) causes a decline in cognitive function that poses a significant hazard to human health. However, the exact pathogenesis of AD and effective treatment have both proven elusive. Circular RNAs (circRNAs), which were initially deemed as meaningless non-coding RNAs, have been shown to participate in a variety of physiological and pathological processes. However, the variations and characteristics of circRNAs are not fairly well understood during the occurrence and development of AD.MethodsIn this study, we performed RNA sequencing analyses, identified circRNA expression profiles, and explored the circRNA-associated competing endogenous RNA (ceRNA) relationship in the hippocampus of five familial AD (5 × FAD) mice with cognitive dysfunction.ResultsThe RNA sequencing results identified 34 dysregulated circRNAs in the hippocampus of 5 × FAD mice, including 17 upregulated and 17 downregulated circRNAs. The circRNA-miRNA interaction network for the dysregulated circRNAs was generated, and it was found to include 34 circRNAs and 711 miRNAs. Next, 2067 mRNAs potentially modulated by upregulated circRNA-interacting miRNAs and 2297 mRNAs potentially modulated by downregulated circRNA-interacting miRNAs were identified. Pathway enrichment analyses revealed that the circRNA-miRNA-mRNA network modulated AD development via multiple pathways, such as axon guidance, mitogen-activated protein kinase, and neurotrophin. The associated biological processes were mainly related to neuron projection development, cell morphogenesis, and head development. Their corresponding distributions were especially high in the axon, postsynapse, and neuronal body. We constructed a ceRNA network that included five circRNAs, four miRNAs, and 188 mRNAs. In this network, the differential expressions of three circRNAs (circRNA04655, circRNA00723, and circRNA01891), two miRNAs (miR-3470b and miR-6240), and 13 mRNAs (Vgll3, Nhsl2, Rab7, Tardbp, Vps33b, Fam107a, Tacr1, Ankrd40, Creb1, Snap23, Csnk1a1, Bmi1, and Bfar) in the hippocampus of 5 × FAD mice using qRT-PCR analyses were consistent with the RNA sequencing results. Another one circRNAs (circRNA00747) and two mRNAs (Zfp37 and Polr1e) had similar expression trends to the sequencing data, while circRNA03723 and Mapk10 had deviated expression trends to the sequencing data.ConclusionsIn conclusion, our study uncovered dysregulated circRNA expression profiles in the hippocampus of 5 × FAD mice, stretched comprehension of ceRNA biology, investigated the potential role of this ceRNA network in pathogenesis and progression, and identified potential biomarkers and therapeutic targets for AD.

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Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

Sun

Zeng

Cai

et al. 2022

Front. Aging Neurosci.

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“…Aberrant tau hyperphosphorylation and aggregate formation in AD is reportedly mediated by miRNA networks, as supported by a new report on miR-23b-3p. Jiang et al, showed that miR-23b-3p targets glycogen synthase kinase-3β (GSK-3β) to prevent tau hyperphosphorylation in vitro as well as in an AD mouse model (APP/PS1 mice) [ 100 ]. Moreover, in vivo delivery of miR-23-3p restored cognitive decline in the model while inhibiting neuronal apoptosis, Aβ 1-42 generation, and tau hyperphosphorylation in a neuroprotective role.…”

Section: Mechanisms Of Mirnas In Dementia-related Diseasementioning

confidence: 99%

MicroRNA Networks in Cognition and Dementia

Blount

Coursey

Kocerha

2022

Cells

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The change from viewing noncoding RNA as “junk” in the genome to seeing it as a critical epigenetic regulator in almost every human condition or disease has forced a paradigm shift in biomedical and clinical research. Small and long noncoding RNA transcripts are now routinely evaluated as putative diagnostic or therapeutic agents. A prominent role for noncoding microRNAs in the central nervous system has uncovered promising new clinical candidates for dementia-related disorders, treatments for which currently remain elusive even as the percentage of diagnosed patients increases significantly. Cognitive decline is a core neurodegenerative process in Alzheimer’s Disease, Frontotemporal Dementia, Lewy body dementia, vascular dementia, Huntington’s Disease, Creutzfeldt–Jakob disease, and a significant portion of Parkinson’s Disease patients. This review will discuss the microRNA-associated networks which influence these pathologies, including inflammatory and viral-mediated pathways (such as the novel SARS-CoV-2 virus implicated in COVID-19), and their current status in clinical trials.

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“…Moreover, cGMP directly inactivates a kinase enzyme known as phosphorylated glycogen synthase kinase-3β-(Ser9) (pGSK3β-Ser9), and in turn phosphosphorylation of Tau (pTau) decreases ( García-Osta et al, 2012 ). The reduction in the phosphorylation of pTau elicits the protection of neurons and eventually enhances cognitive function ( Jiang et al, 2022 ). Vinpocetine has been used for a long time to treat dementia by selectively inhibiting PDE1 ( Shekarian et al, 2020a ; Dubey et al, 2020 ).…”

Section: Pde1 and Camp/pka/creb/bdnf And Cgmp/pkg/creb/bdnf Pathwaysmentioning

confidence: 99%

The role of Phosphodiesterase-1 and its natural product inhibitors in Alzheimer’s disease: A review

et al. 2022

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Phosphodiesterase-1 (PDE1) is a versatile enzyme that has surprisingly received considerable attention as a possible therapeutic target in Alzheimer’s disease (AD) because it maintains the homeostasis of 3ʹ,5ʹ-cyclic adenosine monophosphate (cAMP) and 3ʹ,5ʹ-cyclic guanosine monophosphate (cGMP) in the brain. 3ʹ,5ʹ-cyclic adenosine monophosphate and 3ʹ,5ʹ-cyclic guanosine monophosphate are the two key second messengers that regulate a broad range of intracellular processes and neurocognitive functions, specifically memory and cognition, associated with Alzheimer’s disease. However, the lack of available selective drugs on the market poses challenges to identifying the beneficial effects of natural products. The present review focuses on Phosphodiesterase-1 and its isoforms, splicing variants, location, distribution, and function; the role of Phosphodiesterase-1 inhibitors in Alzheimer’s disease; and the use of vinpocetine and natural products as specific Phosphodiesterase-1 inhibitors. Moreover, it aims to provide ongoing updates, identify research gaps, and present future perspectives. This review indicates the potential role of Phosphodiesterase-1 inhibitors in the treatment of neurodegenerative disorders, such as Alzheimer’s disease. Certain clinical trials on the alleviation of Alzheimer’s disease in patients are still in progress. Among de novo outcomes, the employment of Phosphodiesterase-1 inhibitors to treat Alzheimer’s disease is an important advancement given the absence of particular therapies in the pipeline for this highly prevalent disease. To sum up, Phosphodiesterase-1 inhibition has been specifically proposed as a critical therapeutic approach for Alzheimer’s disease. This study provides a comprehensive review on the biological and pharmacological aspects of Phosphodiesterase-1, its role on the Alzheimer’s diseases and its significance as Alzheimer’s disease therapeutic target in drug discovery from natural products. This review will help clinical trials and scientific research exploring new entities for the treatment and prevention of Alzheimer’s disease.

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miR-23b-3p rescues cognition in Alzheimer’s disease by reducing tau phosphorylation and apoptosis via GSK-3β signaling pathways

Cited by 32 publications

References 64 publications

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

MicroRNA Networks in Cognition and Dementia

The role of Phosphodiesterase-1 and its natural product inhibitors in Alzheimer’s disease: A review

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