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MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer

The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and...

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Autores principales: Godlewski, Jakub, Lenart, Jacek, Salinska, Elzbieta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468660/
https://www.ncbi.nlm.nih.gov/pubmed/30813461
http://dx.doi.org/10.3390/ncrna5010020
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author Godlewski, Jakub
Lenart, Jacek
Salinska, Elzbieta
author_facet Godlewski, Jakub
Lenart, Jacek
Salinska, Elzbieta
author_sort Godlewski, Jakub
collection PubMed
description The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain.
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spelling pubmed-64686602019-04-19 MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer Godlewski, Jakub Lenart, Jacek Salinska, Elzbieta Noncoding RNA Review The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain. MDPI 2019-02-23 /pmc/articles/PMC6468660/ /pubmed/30813461 http://dx.doi.org/10.3390/ncrna5010020 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Godlewski, Jakub
Lenart, Jacek
Salinska, Elzbieta
MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title_full MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title_fullStr MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title_full_unstemmed MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title_short MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer
title_sort microrna in brain pathology: neurodegeneration the other side of the brain cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468660/
https://www.ncbi.nlm.nih.gov/pubmed/30813461
http://dx.doi.org/10.3390/ncrna5010020
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