Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions

Bibliographic Details
Title: Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions
Authors: Claudia Strafella, Valerio Caputo, Andrea Termine, Francesca Assogna, Clelia Pellicano, Francesco E. Pontieri, Lucia Macchiusi, Giulietta Minozzi, Stefano Gambardella, Diego Centonze, Paola Bossù, Gianfranco Spalletta, Carlo Caltagirone, Emiliano Giardina, Raffaella Cascella
Source: Frontiers in Genetics, Vol 12 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Genetics
Subject Terms: Parkinson’s disease, genetics, susceptibility, IL6, therapeutic target, miRNA, Genetics, QH426-470
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-8021
Relation: https://www.frontiersin.org/articles/10.3389/fgene.2021.651971/full; https://doaj.org/toc/1664-8021
DOI: 10.3389/fgene.2021.651971
Access URL: https://doaj.org/article/729f45a74cc44bca91ecb69c8b1f0ed7
Accession Number: edsdoj.729f45a74cc44bca91ecb69c8b1f0ed7
Database: Directory of Open Access Journals
More Details
ISSN:16648021
DOI:10.3389/fgene.2021.651971
Published in:Frontiers in Genetics
Language:English