miR-34a-5p and miR-125b-5p attenuate Aβ-induced neurotoxicity through targeting BACE1

Li, Pengxiang; Xu, Ying; Wang, Baiping; Huang, Jiana; Li, Qiang

doi:10.1016/j.jns.2020.116793

Cited by 58 publications

(53 citation statements)

References 37 publications

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“…The same study also reported that miRNA-125b and BACE1 mRNA serum expression levels were respectively reduced and increased in patients with sporadic AD compared to age-matched healthy individuals. A negative correlation between miRNA-125b and BACE1 mRNA serum expression levels was found in AD patients 51 .…”

Section: Discussionmentioning

confidence: 94%

“…In an attempt to address our results from an overarching neurobiological standpoint, we outline that miRNA-125b is the miRNA more extensively investigated in the AD human brain and biofluids and experimental models of the disease as well. Studies conducted in primary mouse cortical neurons (MCN) and neuroblastoma Neuro2a (N2a) cells show that miRNA-125b binds to the BACE1 protein with an inhibitory effect on its expression levels and mitigates Aβ-induced neurotoxicity 51 . In particular, BACE1 protein acted as a target of miRNA-125b and was negatively modulated by this miRNA in both MCN and N2a cells.…”

Section: Discussionmentioning

confidence: 99%

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MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

Vergallo

Zhao²,

Lemercier³

et al. 2021

Transl Psychiatry

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There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer’s disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD. Second, we investigated the impact of age, sex, and the Apolipoprotein E ε4 (APOE ε4) allele, on the identified miRNA plasma concentrations. In addition, we explored the cross-sectional and longitudinal association of the miRNAs plasma concentrations with regional brain metabolic uptake using amyloid-β (Aβ)-positron emission tomography (Aβ-PET) and 18F-fluorodeoxyglucose-PET (18F-FDG-PET). We identified a set of six brain-enriched miRNAs—miRNA-125b, miRNA-146a, miRNA-15b, miRNA-148a, miRNA-26b, and miRNA-100. Age, sex, and APOE ε4 allele were not associated with individual miRNA abundance. MiRNA-15b concentrations were significantly lower in the Aβ-PET-positive compared to Aβ-PET-negative individuals. Furthermore, we found a positive effect of the miRNA-15b*time interaction on regional metabolic 18F-FDG-PET uptake in the left hippocampus. Plasma miRNA-125b concentrations, as well as the miRNA-125b*time interaction (over a 2-year follow-up), were negatively associated with regional Aβ-PET standard uptake value ratio in the right anterior cingulate cortex. At baseline, we found a significantly negative association between plasma miRNA-125b concentrations and 18F-FDG-PET uptake in specific brain regions. In an asymptomatic at-risk population for AD, we show significant associations between plasma concentrations of miRNA-125b and miRNA-15b with core neuroimaging biomarkers of AD pathophysiology. Our results, coupled with existing experimental evidence, suggest a potential protective anti-Aβ effect of miRNA-15b and a biological link between miRNA-125b and Aβ-independent neurotoxic pathways.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

Vergallo

Zhao²,

Lemercier³

et al. 2021

Transl Psychiatry

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“…By exploring changes in microRNA expression profiles, Hébert et al discovered that the miR-29a/b-1 cluster inhibited the expression of endogenous BACE1 and was markedly reduced in sporadic AD [ 96 ]. Meanwhile, a recent study has revealed that addition of microRNA-34a-5p or microRNA-125b-5p attenuates A β -induced neurotoxicity via targeting BACE1 [ 97 ]. Additionally, Li et al have unveiled that overexpression of microRNA-219-5p contributes to tau phosphorylation in brain tissue from AD patients [ 98 ].…”

Section: Epigenetic In Neurodegenerative Disordersmentioning

confidence: 99%

Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

Wang

Liu

et al. 2021

Neural Plasticity

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Microglia-mediated neuroinflammation is one of the most remarkable hallmarks of neurodegenerative diseases (NDDs), including AD, PD, and ALS. Accumulating evidence indicates that microglia play both neuroprotective and detrimental roles in the onset and progression of NDDs. Yet, the specific mechanisms of action surrounding microglia are not clear. Modulation of microglia function and phenotypes appears to be a potential strategy to reverse NDDs. Until recently, research into the epigenetic mechanisms of diseases has been gradually developed, making it possible to elucidate the molecular mechanisms underlying the epigenetic regulation of microglia in NDDs. This review highlights the function and phenotypes of microglia, elucidates the relationship between microglia, epigenetic modifications, and NDDs, as well as the possible mechanisms underlying the epigenetic modulation of microglia in NDDs with a focus on potential intervention strategies.

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“…Another recent study shows that microRNA-298 represses the expression of BACE1, APP, Aβ40, and Aβ42 in the cell model, suggesting that microRNA-298 may be a therapeutic target for AD (120). Meanwhile, the addition of microRNA-34a-5p and microRNA-125b-5p reduces Aβ by targeting BACE1 (121). Abnormally phosphorylated tau protein is another key pathological hallmark of AD.…”

Section: Non-coding Rnas In Admentioning

confidence: 99%

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

2020

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miR-34a-5p and miR-125b-5p attenuate Aβ-induced neurotoxicity through targeting BACE1

Cited by 58 publications

References 37 publications

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

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