MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis
Articolo
Data di Pubblicazione:
2016
Citazione:
MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis / D. Lecca, D. Marangon, G.T. Coppolino, A.M. Méndez, A. Finardi, G.D. Costa, V. Martinelli, R. Furlan, M.P. Abbracchio. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6(2016 Oct 04). [10.1038/srep34503]
Abstract:
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
multidisciplinary
Elenco autori:
D. Lecca, D. Marangon, G.T. Coppolino, A.M. Méndez, A. Finardi, G.D. Costa, V. Martinelli, R. Furlan, M.P. Abbracchio
Link alla scheda completa:
Link al Full Text: