MicroRNA-135a and -200b, potential Biomarkers for Alzheimer׳s disease, regulate β secretase and amyloid precursor protein

Liu, Chen-Geng; Wang, Jinling; Li, Lei; Xue, Lixiang; Zhang, Yueqi; Wang, Peichang

doi:10.1016/j.brainres.2014.04.026

Cited by 96 publications

(80 citation statements)

References 39 publications

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“…The present study revealed that the expression levels of miR-135b were significantly decreased in the peripheral blood of AD patients compared with those of the age-matched normal controls, suggesting that serum miR-135b levels may be used for the clinical diagnosis of AD. In agreement with the findings of the present study, Liu et al analyzed the miR hippocampi expression profiles of APP/PS1 transgenic and wild-type mice, and observed that miR-135a was significantly downregulated in the hippocampi of the transgenic mice compared with those of the wild type mice (11). Therefore, miR-135a and miR-135b may both participate in the development and progression of AD.…”

Section: Discussionsupporting

confidence: 91%

“…Denk et al investigated the expression profiling of 1,178 miRs in cerebrospinal fluid samples from patients with AD and normal controls, and discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD by positively classifying controls and AD cases with 96.4 and 95.5% accuracy, respectively (8). Furthermore, Lei et al reported that the downregulation of miR-29c was correlated with increased BACE1 expression levels in sporadic Alzheimer's disease (4 in the hippocampi of transgenic and wild-type mice, and identified that miR-135a was significantly downregulated in the hippocampi of APP/PS1 transgenic mice compared with the wild-type control, suggesting that downregulation of miR-135a may have a role in the development of AD (11). However, the exact role of miR-135b in AD still remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

Zhang

Xing

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs (miRs) are a class of endogenous small non-coding RNAs that have been revealed to negatively mediate the expression of their target genes at the post-transcriptional level. Recently, particular miRs have demonstrated an involvement in the pathogenesis of Alzheimer's disease (AD). However, the specific role of miR-135b in AD has yet to be elucidated. The present study aimed to investigate the neuroprotective role of miR-135b, in addition to its underlying mechanism. Herein, reverse transcription-quantitative polymerase chain reaction was conducted to determine miR-135b expression levels in the peripheral blood samples of patients with AD and age-matched normal controls. The data of the present study revealed that the expression levels of miR-135b were significantly reduced in the peripheral blood of AD patients compared with normal controls (P<0.01). In vitro MTT analyses identified that the overexpression of miR-135b significantly enhanced the proliferation of hippocampal cells (P<0.01). Furthermore, in vivo analysis using a Y-maze test indicated that injection with miR-135b mimics into the third ventricle of anesthetized SAMP8 mice significantly enhanced their learning and memory capacities (P<0.01). Molecular mechanism investigations identified β-site APP-cleaving enzyme 1 (BACE1) as a direct target gene of miR-135b, and the latter was identified to negatively mediate the protein expression levels of BACE1 in hippocampal cells, in addition to hippocampal tissues, of SAMP8 mice. Based on the aforementioned findings, we propose that miR-135b has a neuroprotective role via direct targeting of BACE1 and, thus, may be used for the treatment of AD.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

Zhang

Xing

Guo

et al. 2016

Experimental and Therapeutic Medicine

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“…The source of miRNAs is another important aspect. So far different blood sources were investigated for detection of circulating miRNAs in AD patients: plasma [21, 31, 34, 35, 38, 46, 87], serum [20, 24, 25, 27, 32, 33, 36, 40–43], blood mononuclear cells [30], whole blood [22, 84–86] and plasma exosomes [29]. All miRNA sources have some advantages and disadvantages.…”

Section: Discussionmentioning

confidence: 99%

Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

et al. 2017

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Alzheimers disease (AD) is the most common age-related dementia. Among its major challenges is identifying molecular signatures characteristic for the early AD stage in patients with Mild Cognitive Impairment (MCI-AD), which could serve for deciphering the AD pathomechanism and also as non-invasive, easy-to-access biomarkers. Using qRT-PCR we compared the microRNA (miRNA) profiles in blood plasma of 15 MCI-AD patients, whose diagnoses were confirmed by cerebrospinal fluid (CSF) biomarkers, with 20 AD patients and 15 non-demented, age-matched individuals (CTR).To minimize methodological variability, we adhered to standardization of blood and CSF assays recommended by the international Joint Programming for Neurodegenerative Diseases (JPND) BIOMARKAPD consortium, and we employed commercially available Exiqon qRT-PCR-assays. In the first screening, we assessed 179 miRNAs of plasma. We confirmed 23 miRNAs reported earlier as AD biomarker candidates in blood and found 26 novel differential miRNAs between AD and control subjects. For representative 15 differential miRNAs, the TargetScan, MirTarBase and KEGG database analysis indicated putative protein targets among such AD hallmarks as MAPT (Tau), proteins involved in amyloidogenic proteolysis, and in apoptosis. These 15 miRNAs were verified in separate, subsequent subject groups. Finally, 6 miRNAs (3 not yet reported in AD context and 3 reported in AD blood) were selected as the most promising biomarker candidates differentiating early AD from controls with the highest fold changes (from 1.32 to 14.72), consistent significance, specificities from 0.78 to 1 and sensitivities from 0.75 to 1. (patent pending, PCT/IB2016/052440).

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“…Because of the pivotal role that miRNAs play in complex neurological diseases, there has been over the past recent years a push to exploit them in order to understand better the brain and its dysfunctions. miRNAs are also used to identify potential new therapeutic targets and to identify new biomarkers for neurodevelopmental and neurodegenerative diseases (Cogoni, Ruberti, & Barbato, 2015;Grasso, Piscopo, Confaloni, & Denti, 2014;Liu et al, 2014;Mundalil Vasu et al, 2014;Wang, Wang, Yang, & Huang, 2014).…”

Section: Micrornas Regulator Of Neural Cell Function: a Pivotal Rolementioning

confidence: 99%

MicroRNAs

Guibinga¹

2015

Advances in Genetics

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MicroRNA-135a and -200b, potential Biomarkers for Alzheimer׳s disease, regulate β secretase and amyloid precursor protein

Cited by 96 publications

References 39 publications

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

MicroRNAs

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