Circulating microRNAs in Huntington’s disease: Emerging mediators in metabolic impairment

Díez-Planelles, Carlos; Sánchez-Lozano, P.; Crespo, M. Carmen; Gil-Zamorano, Judit; Ribacoba, René; González, Nieves; Suárez, Emma; Martinez-Descals, Asunción; Martínez‐Camblor, Pablo; Álvarez, Victoria; Martín‐Hernández, Roberto; Huerta-Ruíz, I.; González-Garcı́a, Inés; Cosgaya, José Miguel; Visioli, Francesco; Dávalos, Alberto; Iglesias‐Gutiérrez, Eduardo; Tomás-Zapico, Cristina

doi:10.1016/j.phrs.2016.05.005

Cited by 71 publications

(58 citation statements)

References 83 publications

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“…Some of these circulating miRNAs have already been found in other neurodegenerative disorders. For example, miR-128-3p was found overexpressed in plasma from people with Huntington’s disease 27 and in T cells from people with multiple sclerosis 28 . In contrast, lower levels of miR-142-3p were found in plasma of patients with Alzheimer’s disease than in controls 29 .…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s ataxia patients

Seco-Cervera

González-Rodríguez

Ibáñez-Cabellos

et al. 2017

Sci Rep

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MicroRNAs (miRNAs) are noncoding RNAs that contribute to gene expression modulation by regulating important cellular pathways. In this study, we used small RNA sequencing to identify a series of circulating miRNAs in blood samples taken from Friedreich's ataxia patients. We were thus able to develop a miRNA biomarker signature to differentiate Friedreich's ataxia (FRDA) patients from healthy people. Most research on FDRA has focused on understanding the role of frataxin in the mitochondria, and a whole molecular view of pathological pathways underlying FRDA therefore remains to be elucidated. We found seven differentially expressed miRNAs, and we propose that these miRNAs represent key mechanisms in the modulation of several signalling pathways that regulate the physiopathology of FRDA. If this is the case, miRNAs can be used to characterize phenotypic variation in FRDA and stratify patients' risk of cardiomyopathy. In this study, we identify miR-323-3p as a candidate marker for phenotypic differentiation in FRDA patients suffering from cardiomyopathy. We propose the use of dynamic miRNAs as biomarkers for phenotypic characterization and prognosis of FRDA.Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia in people of European descent, affecting around 2-5 people in every 100,000 (Orphanet reports). This rare, childhood-onset disease is characterized by a progressive loss of sensory neurons in the dorsal root ganglia (DRG) and posterior columns. This loss of neurons is followed by degeneration of corticospinal and spinocerebellar tracts of the spinal cord, culminating in gait and limb ataxia, loss of tendon reflexes and dysarthria 1, 2 . The cerebellar dentate nucleus is also affected 3 . Other non-neurological features of FRDA are scoliosis, diabetes and cardiac symptoms [4][5][6] . Hypertrophic cardiomyopathy, which is found in two thirds of FRDA patients at the time of diagnosis, is the primary cause of death in these patients 7,8 . FRDA is most often caused by a homozygous GAA repeat expansion mutation (typically between 600 and 1200 repeats) in the first intron of the frataxin gene (FXN), which is found on chromosome 9q21.11 and encodes the protein frataxin 2, 9 . The elevated number of GAA repeats and resulting blockage effects on the RNAPII transcription machinery ("sticky DNA", hairpin structures, parallel duplex structures, R-loops, etc.; reviewed in ref. 10) have been proposed as causes of decreased expression of the mitochondrial protein frataxin 11 . The frataxin

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Section: Discussionmentioning

confidence: 99%

Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s ataxia patients

Seco-Cervera

González-Rodríguez

Ibáñez-Cabellos

et al. 2017

Sci Rep

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“…Outside of the CNS, significant alterations in miRNA expression have also been detected in extracellular fluids in HD and other polyQ disorders [148][149][150][151]. For example, miR-10b-5p [148,150] and miR-34b [149] were shown to be significantly elevated in the plasma of HD patients and HD asymptomatic gene carriers, respectively.…”

Section: Cmirnas Dysregulation In Polyq Disordersmentioning

confidence: 99%

“…Most recently, cmiRNAs analysis of plasma samples from 15 HD symptomatic patients shows that 168 cmiRNAs are altered. Most of upregulated miRNAs in HD patients are involved in metabolism regulation [151]. In SCA3, four miRNAs, including miR-25, miR-125b, miR-29a and miR-34b, are dysregulated in the serums of SCA3/MJD patients, with the first three being decreased and the last being dramatically elevated [147].…”

Section: Cmirnas Dysregulation In Polyq Disordersmentioning

confidence: 99%

Welcome to the 10th volume of Epigenomics

Martin

2018

Epigenomics

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“…Of the 752 mature human microRNAs, 168 microRNAs were found to be altered in circulating plasma samples from symptomatic patients (82). Other research groups identified different altered microRNA profiles in HD models or patients.…”

Section: Epigenetic Changes In Aging-related Neurodegenerative Diseasesmentioning

confidence: 99%

Age-related epigenetic regulation in the brain and its role in neuronal diseases

Kim-Ha¹,

Kim²

2016

BMB Reports

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Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

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Circulating microRNAs in Huntington’s disease: Emerging mediators in metabolic impairment

Cited by 71 publications

References 83 publications

Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s ataxia patients

Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s ataxia patients

Welcome to the 10th volume of Epigenomics

Age-related epigenetic regulation in the brain and its role in neuronal diseases

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