MicroRNA-149 is downregulated in Alzheimer’s disease and inhibits β-amyloid accumulation and ameliorates neuronal viability through targeting BACE1

Du, Wei; Lei, Chengbin; Dong, Yong

doi:10.1590/1678-4685-gmb-2020-0064

Cited by 19 publications

(13 citation statements)

References 32 publications

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“…Additionally, miR-18a may have a role in abnormal gene expression detected in the senescence-accelerated mouse-prone 8 (SAMP8) model of sporadic AD [ 41 ]. MiR-149-5p may regulate Aβ1-42 deposition and have neuroprotective effects by directly targeting BACE1 [ 42 ]. MiR-149-5p also has a role in Parkinson’s disease, particularly in the prevention of cellular death and rupture of the blood-brain barrier [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

Manzini

Rivabene

Crestini

et al. 2022

IJMS

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The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.

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Section: Discussionmentioning

confidence: 99%

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

Manzini

Rivabene

Crestini

et al. 2022

IJMS

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“…Circulating miRNAs exist in serum and plasma and are stably expressed, which provides the possibility for clinical detection of miRNA expression and content changes [18]. In AD patients, several miRNAs have been identified to be differentially expressed in both serum and plasma of patients and may serve as potential biomarkers for clinical diagnosis of AD, such as miR-149 and miR-328-5p [19, 20].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

Zhang

Liu

Teng

et al. 2021

Neuroimmunomodulation

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Introduction: This study aimed to explore the diagnostic value and effect of miR-381-3p on Alzheimer’s disease (AD). Methods: RT-qPCR was used for the measurement of miR-381-3p levels. Pearson correlation coefficient was used for the correlation analysis. Receiver operating characteristic (ROC) curve was constructed to assess the distinct ability of miR-381-3p for AD. SH-SY5Y cells were treated with Aβ25-35 to establish an AD cell model. The role of miR-381-3p on cell proliferation and apoptosis was detected. ELISA was applied to detect the protein levels of inﬂammatory cytokine expression. The target relationship of miR-381-3p with PTGS2 was verified by luciferase reporter gene assay. Results: Low expression of miR-381-3p was detected in the serum of AD patients and cell models. There was a negative association of serum miR-381-3p with the serum inflammatory cytokines. The ROC curve demonstrated the distinct ability of serum miR-381-3p for AD, with the AUC value of 0.898, with a sensitivity of 87.5%, and a specificity of 77.7%. Overexpression of miR-381-3p reversed the influence of Aβ25-35 on cell proliferation and apoptosis, but miR-381-3p downregulation exacerbated the influence. miR-381-3p overexpression inhibited the release of IL-6, IL-1β, and TNF-α induced by Aβ25-35 treatment, whereas miR-381-3p downregulation further promoted the release of inflammatory cytokines. PTGS2 was the target gene of miR-381-3p and was upregulated in AD cell models. Conclusion: miR-381-3p is less expressed in the serum of AD patients and has potential diagnostic values for AD. Overexpression of miR-381-3p may attenuate Aβ25-35-induced neurotoxicity and inflammatory responses via targeting PTGS2 in SH-SY5Y cells.

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“…Bioinformatics analyses have also demonstrated therapeutic potentials for Lupeol and several compounds extracted from Cajanus cajan and Citrus reticulata by the inhibition of BACE1 in situ ( Koirala et al, 2017 ; Adewole and Ishola, 2021 ). Moreover, miRNAs, such as miR-34a-5p, miR-125b-5p, miR-15b, and miR-149, have been demonstrated in distinctive studies to inhibit BACE1 expression, decrease amyloid accumulation, and ameliorate neuronal injury ( Gong et al, 2017 ; Li P. et al, 2020 ; Du et al, 2021 ). Overall, although the precise mechanism of action is not elucidated, however, BACE1-AS as a lncRNA is reportedly involved in the pathophysiology of AD rather than another disease, which is believed to play a role via the regulation of mRNA stability and expression of BACE1 β-Secretase.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The Emerging Roles of the β-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer

Sayad

Najafi

Hussen

et al. 2022

Front. Aging Neurosci.

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The β-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer’s disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson’s disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.

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MicroRNA-149 is downregulated in Alzheimer’s disease and inhibits β-amyloid accumulation and ameliorates neuronal viability through targeting BACE1

Cited by 19 publications

References 32 publications

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

The Emerging Roles of the β-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer

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