miR-30a-5p induces Aβ production via inhibiting the nonamyloidogenic pathway in Alzheimer’s disease

Sun, Ting; Zhao, Kaiyue; Liu, Mimin; Cai, Zhongdi; Zeng, Li; Zhang, Junxia; Li, Rui

doi:10.1016/j.phrs.2022.106153

Cited by 31 publications

(21 citation statements)

References 55 publications

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“…The MWM test was used to examine the spatial learning and memory activities of 5×FAD and WT mice. The test procedure was the same as described in our previous studies [ 40 , 41 ]. Briefly, the MWM test is divided into two parts: a spatial learning trial and a probe trial.…”

Section: Methodsmentioning

confidence: 99%

The Relationship between the Aberrant Long Non-Coding RNA-Mediated Competitive Endogenous RNA Network and Alzheimer’s Disease Pathogenesis

Cai

Zhao

Zeng

et al. 2022

IJMS

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Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by cognitive dysfunction. The role of long non-coding RNAs (lncRNAs) with the action of competitive endogenous RNA (ceRNA) in AD remains unclear. The present study aimed to identify significantly differentially expressed lncRNAs (SDELs) and establish lncRNA-associated ceRNA networks via RNA sequencing analysis and a quantitative real-time Polymerase Chain Reaction (qPCR) assay using transgenic mice with five familial AD mutations. A total of 53 SDELs in the cortex and 51 SDELs in the hippocampus were identified, including seven core SDELs common to both regions. The functions and pathways were then investigated through the potential target genes of SDELs via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, which indicate biological effects, action distributions, and pathological transductions associated with AD. Based on the ceRNA hypothesis, integrated ceRNA networks in the cortex and hippocampus of lncRNA-miRNA-mRNA were constructed. The core SDEL-mediated ceRNA relationship was established and the expression of these RNAs was verified by qPCR. The results identified lncRNA ENSMUST00000127786 and highlighted miRNAs and mRNAs as potential key mediators in AD. These findings provide AD-derived lncRNA-mediated ceRNA profiles, and further experimental evidence is needed to confirm these identified ceRNA regulatory relationships.

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Section: Methodsmentioning

confidence: 99%

The Relationship between the Aberrant Long Non-Coding RNA-Mediated Competitive Endogenous RNA Network and Alzheimer’s Disease Pathogenesis

Cai

Zhao

Zeng

et al. 2022

IJMS

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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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“…However, the detailed molecular mechanisms by which mitochondrial dysfunction affects neurodegeneration remain largely unknown. RNAs (circRNAs), are implicated in mitochondrial dysfunction and mitochondrion associated signaling transduction (du Mee et al, 2020;Zeng et al, 2021;Sun et al, 2022a;Jiang et al, 2022). A small proportion of ncRNAs found in mitochondria are reportedly transcribed from the mitochondrial genome, while the majority are nuclear-encoded ncRNAs that enter the mitochondria from the nucleus (Sharma et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases

et al. 2023

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Neurodegenerative diseases (NDs) are common chronic disorders associated with progressive nervous system damage, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, among others. Mitochondria are abundant in various nervous system cells and provide a bulk supply of the adenosine triphosphate necessary for brain function, considered the center of the free-radical theory of aging. One common feature of NDs is mitochondrial dysfunction, which is involved in many physiopathological processes, including apoptosis, inflammation, oxidative stress, and calcium homeostasis. Recently, genetic studies revealed extensive links between mitochondrion impairment and dysregulation of non-coding RNAs (ncRNAs) in the pathology of NDs. Traditional Chinese medicines (TCMs) have been used for thousands of years in treating NDs. Numerous modern pharmacological studies have demonstrated the therapeutic effects of prescription, herbal medicine, bioactive ingredients, and monomer compounds of TCMs, which are important for managing the symptoms of NDs. Some highly effective TCMs exert protective effects on various key pathological features regulated by mitochondria and play a pivotal role in recovering disrupted signaling pathways. These disrupted signaling pathways are induced by abnormally-expressed ncRNAs associated with mitochondrial dysfunction, including microRNAs, long ncRNAs, and circular RNAs. In this review, we first explored the underlying ncRNA mechanisms linking mitochondrial dysfunction and neurodegeneration, demonstrating the implication of ncRNA-induced mitochondrial dysfunction in the pathogenesis of NDs. The ncRNA-induced mitochondrial dysfunctions affect mitochondrial biogenesis, dynamics, autophagy, Ca2+ homeostasis, oxidative stress, and downstream apoptosis. The review also discussed the targeting of the disease-related mitochondrial proteins in NDs and the protective effects of TCM formulas with definite composition, standardized extracts from individual TCMs, and monomeric compounds isolated from TCM. Additionally, we explored the ncRNA regulation of mitochondrial dysfunction in NDs and the effects and potential mechanisms of representative TCMs in alleviating mitochondrial pathogenesis and conferring anti-inflammatory, antioxidant, and anti-apoptotic pathways against NDs. Therefore, this review presents an overview of the role of mitochondrion-related ncRNAs and the target genes for TCM-based therapeutic interventions in NDs, providing insight into understanding the “multi-level compound-target-pathway regulatory” treatment mechanism of TCMs.

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miR-30a-5p induces Aβ production via inhibiting the nonamyloidogenic pathway in Alzheimer’s disease

Cited by 31 publications

References 55 publications

The Relationship between the Aberrant Long Non-Coding RNA-Mediated Competitive Endogenous RNA Network and Alzheimer’s Disease Pathogenesis

The Relationship between the Aberrant Long Non-Coding RNA-Mediated Competitive Endogenous RNA Network and Alzheimer’s Disease Pathogenesis

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

Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases

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