microRNA profiling: increased expression of miR-147a and miR-518e in progressive supranuclear palsy (PSP)

Tatura, Roman; Buchholz, Malte; Dickson, Dennis W.; Swieten, John van; McLean, Catriona; Höglinger, Günter U.; Müller, Ulrich

doi:10.1007/s10048-016-0480-6

Cited by 22 publications

(14 citation statements)

References 20 publications

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“…Among environmental factors, advanced age is the best established risk factor 6 . Epigenetic modifications reported so far in PSP include aberrant DNA methylation at the MAPT locus 7 – 9 and miRNA dysregulation 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1

et al. 2018

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Genetic, epigenetic, and environmental factors contribute to the multifactorial disorder progressive supranuclear palsy (PSP). Here, we study epigenetic changes by genome-wide analysis of DNA from postmortem tissue of forebrains of patients and controls and detect significant (P < 0.05) methylation differences at 717 CpG sites in PSP vs. controls. Four-hundred fifty-one of these sites are associated with protein-coding genes. While differential methylation only affects a few sites in most genes, DLX1 is hypermethylated at multiple sites. Expression of an antisense transcript of DLX1, DLX1AS, is reduced in PSP brains. The amount of DLX1 protein is increased in gray matter of PSP forebrains. Pathway analysis suggests that DLX1 influences MAPT-encoded Tau protein. In a cell system, overexpression of DLX1 results in downregulation of MAPT while overexpression of DLX1AS causes upregulation of MAPT. Our observations suggest that altered DLX1 methylation and expression contribute to pathogenesis of PSP by influencing MAPT.

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Section: Introductionmentioning

confidence: 99%

Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1

et al. 2018

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“…The expression of miR-132 originally was found to be down-regulated in temporal, parietal, and prefrontal lobes of PSP patients compared to controls [ 48 ]. However, this observation was not confirmed in another study looking at PSP patients and controls [ 49 ]. Based on another report, CSF levels of miR-106b-5p discriminated between PSP and PD patients with a good clinical accuracy [ 50 ].…”

Section: Mirna Dysregulation In Tauopathiesmentioning

confidence: 72%

The Functional Role of microRNAs in the Pathogenesis of Tauopathy

Praticò¹

2020

Cells

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Tauopathies are neurodegenerative disorders which include Alzheimer’s disease, Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy among others. Pathologically, they are characterized by the accumulation of highly phosphorylated and aggregated tau protein in different brain regions. Currently, the mechanisms responsible for their pathogenesis are not known, and for this reason, there is no cure. MicroRNAs (miRNAs) are abundantly present in the central nervous system where they act as master regulators of pathways considered important for tau post-translational modifications, metabolism, and clearance. Although in recent years, several miRNAs have been reported to be altered in tauopathy, we still do not know whether these changes contribute to the onset and progression of the disorder, or are secondary events following the development of tau neuropathology. Additionally, since miRNAs are relatively stable in biological fluids and their measurement is easy and non-invasive, these small molecules hold the potential to function as biomarkers for tauopathy. Herein, we showcase recent findings on the biological link between miRNAs and the pathogenesis of tauopathy, and present emerging evidence supporting their role as biomarkers and targets for novel therapies against them.

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“…In previous studies, the analysis of miRNA expression profiles among patients with PSP showed that miR-132 is specifically downregulated in the brain tissue ( 12 ). miR-147a and miR-518e were also significantly upregulated in the forebrain tissue of patients with PSP ( 13 ). In this study, miR-132 was detected at low levels in the CSF of all participants.…”

Section: Discussionmentioning

confidence: 99%

“…At present, there are very few reports of miRNA expression profiling in PSP. It has been reported that miR-132 ( 12 ), miR-147a, and miR-518e ( 13 ) are expressed in the brain tissues of patients with PSP, but these miRNAs are rarely reported in biofluids. We herein aimed to examine CSF miRNAs, which are thought to be a sensitive indicator of changes in the brain, to elucidate the pathophysiology of PSP and establish specific biomarkers for diagnosis.…”

Section: Introductionmentioning

confidence: 99%