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Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions
The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson’s Disease (PD). In particular, 342 PD patients were subjected to a genotyping ana...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209518/ https://www.ncbi.nlm.nih.gov/pubmed/34149802 http://dx.doi.org/10.3389/fgene.2021.651971 |
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author | Strafella, Claudia Caputo, Valerio Termine, Andrea Assogna, Francesca Pellicano, Clelia Pontieri, Francesco E. Macchiusi, Lucia Minozzi, Giulietta Gambardella, Stefano Centonze, Diego Bossù, Paola Spalletta, Gianfranco Caltagirone, Carlo Giardina, Emiliano Cascella, Raffaella |
author_facet | Strafella, Claudia Caputo, Valerio Termine, Andrea Assogna, Francesca Pellicano, Clelia Pontieri, Francesco E. Macchiusi, Lucia Minozzi, Giulietta Gambardella, Stefano Centonze, Diego Bossù, Paola Spalletta, Gianfranco Caltagirone, Carlo Giardina, Emiliano Cascella, Raffaella |
author_sort | Strafella, Claudia |
collection | PubMed |
description | The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson’s Disease (PD). In particular, 342 PD patients were subjected to a genotyping analysis of a panel of 120 SNPs by Open Array Technology. As control group, 503 samples representative of the European general population were utilized. The genetic analysis identified 26 SNPs associated with PD susceptibility. Of them, 12 SNPs were described as significant expression Quantitative Loci (eQTL) variants in different brain regions associated with motor and non-motor PD phenomenology. Moreover, the study highlighted 11 novel susceptibility genes for PD, which may alter multiple signaling pathways critically involved in peripheral immune response, neuroinflammation, neurodegeneration and dopaminergic neurons wiring. The study of miRNA-target genes highlighted a possible role of miR-499a, miR-196a2, and miR-29a in the modulation of multiple neuroinflammatory and neurodegenerative mechanisms underlying PD physiopathology. The study described a network of interconnected genes (APOE, CLU, IL6, IL7R, IL12B, INPP5D, MAPK1, MEF2C, MIF, and TNFSF14), which may act as upstream regulators in the modulation of biological pathways relevant to PD. Intriguingly, IL6 stands out as a master gene regulator since it may indirectly regulate the network of interconnected genes. The study highlighted different genes and miRNAs interactions potentially involved in PD physiopathology, which are worth to be further explored to improve the knowledge of disease and the research of novel treatments strategies. |
format | Online Article Text |
id | pubmed-8209518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82095182021-06-18 Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions Strafella, Claudia Caputo, Valerio Termine, Andrea Assogna, Francesca Pellicano, Clelia Pontieri, Francesco E. Macchiusi, Lucia Minozzi, Giulietta Gambardella, Stefano Centonze, Diego Bossù, Paola Spalletta, Gianfranco Caltagirone, Carlo Giardina, Emiliano Cascella, Raffaella Front Genet Genetics The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson’s Disease (PD). In particular, 342 PD patients were subjected to a genotyping analysis of a panel of 120 SNPs by Open Array Technology. As control group, 503 samples representative of the European general population were utilized. The genetic analysis identified 26 SNPs associated with PD susceptibility. Of them, 12 SNPs were described as significant expression Quantitative Loci (eQTL) variants in different brain regions associated with motor and non-motor PD phenomenology. Moreover, the study highlighted 11 novel susceptibility genes for PD, which may alter multiple signaling pathways critically involved in peripheral immune response, neuroinflammation, neurodegeneration and dopaminergic neurons wiring. The study of miRNA-target genes highlighted a possible role of miR-499a, miR-196a2, and miR-29a in the modulation of multiple neuroinflammatory and neurodegenerative mechanisms underlying PD physiopathology. The study described a network of interconnected genes (APOE, CLU, IL6, IL7R, IL12B, INPP5D, MAPK1, MEF2C, MIF, and TNFSF14), which may act as upstream regulators in the modulation of biological pathways relevant to PD. Intriguingly, IL6 stands out as a master gene regulator since it may indirectly regulate the network of interconnected genes. The study highlighted different genes and miRNAs interactions potentially involved in PD physiopathology, which are worth to be further explored to improve the knowledge of disease and the research of novel treatments strategies. Frontiers Media S.A. 2021-06-03 /pmc/articles/PMC8209518/ /pubmed/34149802 http://dx.doi.org/10.3389/fgene.2021.651971 Text en Copyright © 2021 Strafella, Caputo, Termine, Assogna, Pellicano, Pontieri, Macchiusi, Minozzi, Gambardella, Centonze, Bossù, Spalletta, Caltagirone, Giardina and Cascella. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Strafella, Claudia Caputo, Valerio Termine, Andrea Assogna, Francesca Pellicano, Clelia Pontieri, Francesco E. Macchiusi, Lucia Minozzi, Giulietta Gambardella, Stefano Centonze, Diego Bossù, Paola Spalletta, Gianfranco Caltagirone, Carlo Giardina, Emiliano Cascella, Raffaella Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title | Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title_full | Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title_fullStr | Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title_full_unstemmed | Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title_short | Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions |
title_sort | immune system and neuroinflammation in idiopathic parkinson’s disease: association analysis of genetic variants and mirnas interactions |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209518/ https://www.ncbi.nlm.nih.gov/pubmed/34149802 http://dx.doi.org/10.3389/fgene.2021.651971 |
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