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000140085 0247_ $$2doi$$a10.1371/journal.pone.0200602
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000140085 041__ $$aEnglish
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000140085 1001_ $$0P:(DE-HGF)0$$aDerkow, Katja$$b0
000140085 245__ $$aDistinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer's disease.
000140085 260__ $$aSan Francisco, California, US$$bPLOS$$c2018
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000140085 520__ $$aMicroRNAs (miRNAs) are non-coding RNAs originally involved in RNA silencing and post-transcriptional regulation of gene expression. We have shown in previous work that the miRNA let-7b can act as a signalling molecule for Toll-like receptor 7, thereby initiating innate immune pathways and apoptosis in the central nervous system. Here, we investigated whether different members of the miRNA family let-7, abundantly expressed in the brain, are released into the human cerebrospinal fluid (CSF) and whether quantitative differences in let-7 copies exist in neurodegenerative diseases. RNA isolated from CSF of patients with Alzheimer´s disease (AD) and from control patients with frontotemporal lobe dementia (FTLD), major depressive episode (MDE) without clinical or neurobiological signs of AD, and healthy individuals, was reverse transcribed with primers against nine let-7 family members, and miRNAs were quantified and analyzed comparatively by quantitative PCR. let-7 miRNAs were present in CSF from patients with AD, FTLD, MDE, and healthy controls. However, the amount of individual let-7 miRNAs in the CSF varied substantially. CSF from AD patients contained higher amounts of let-7b and let-7e compared to healthy controls, while no differences were observed regarding the other let-7 miRNAs. No increase in let-7b and let-7e was detected in CSF from FTLD patients, while in CSF from MDE patients, let-7b and let-7e copy levels were elevated. In CSF from AD patients, let-7b and let-7e were associated with extracellular vesicles. let-7 family members present in the CSF mediated neurotoxicity in vitro, albeit to a variable extent. Taken together, neurotoxic let-7 miRNAs are differentially and specifically released in AD, but also in MDE patients. Thus, these miRNAs may mirror common neuropathological paths and by this serve to unscramble mechanisms of different neurodegenerative diseases.
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000140085 542__ $$2Crossref$$i2018-07-16$$uhttp://creativecommons.org/licenses/by/4.0/
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000140085 650_7 $$2NLM Chemicals$$aMicroRNAs
000140085 650_7 $$2NLM Chemicals$$amirnlet7 microRNA, human
000140085 650_2 $$2MeSH$$aAged
000140085 650_2 $$2MeSH$$aAged, 80 and over
000140085 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000140085 650_2 $$2MeSH$$aCell-Derived Microparticles: metabolism
000140085 650_2 $$2MeSH$$aDepressive Disorder, Major: cerebrospinal fluid
000140085 650_2 $$2MeSH$$aFemale
000140085 650_2 $$2MeSH$$aFrontotemporal Dementia: cerebrospinal fluid
000140085 650_2 $$2MeSH$$aGene Expression Regulation
000140085 650_2 $$2MeSH$$aHumans
000140085 650_2 $$2MeSH$$aMale
000140085 650_2 $$2MeSH$$aMicroRNAs: cerebrospinal fluid
000140085 650_2 $$2MeSH$$aMiddle Aged
000140085 7001_ $$0P:(DE-HGF)0$$aRössling, Rosa$$b1
000140085 7001_ $$0P:(DE-HGF)0$$aSchipke, Carola$$b2
000140085 7001_ $$0P:(DE-HGF)0$$aKrüger, Christina$$b3
000140085 7001_ $$0P:(DE-HGF)0$$aBauer, Jakob$$b4
000140085 7001_ $$0P:(DE-HGF)0$$aFähling, Michael$$b5
000140085 7001_ $$0P:(DE-HGF)0$$aStroux, Andrea$$b6
000140085 7001_ $$0P:(DE-HGF)0$$aSchott, Eckart$$b7
000140085 7001_ $$0P:(DE-HGF)0$$aRuprecht, Klemens$$b8
000140085 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b9$$udzne
000140085 7001_ $$0P:(DE-HGF)0$$aLehnardt, Seija$$b10$$eCorresponding author
000140085 77318 $$2Crossref$$3journal-article$$a10.1371/journal.pone.0200602$$b : Public Library of Science (PLoS), 2018-07-16$$n7$$pe0200602$$tPLOS ONE$$v13$$x1932-6203$$y2018
000140085 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0200602$$gVol. 13, no. 7, p. e0200602 -$$n7$$pe0200602$$q13:7<e0200602 -$$tPLOS ONE$$v13$$x1932-6203$$y2018
000140085 8564_ $$uhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200602
000140085 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047809
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