Cargando…

Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains

Dysregulation of microRNA gene expression has been implicated in many neurodegenerative diseases, including Parkinson’s disease. However, the individual dysregulated microRNAs remain largely unknown. Previous meta-analyses have highlighted several microRNAs being differentially expressed in post-mor...

Descripción completa

Detalles Bibliográficos
Autores principales: Dobricic, Valerija, Schilling, Marcel, Farkas, Ildiko, Gveric, Djordje O, Ohlei, Olena, Schulz, Jessica, Middleton, Lefkos, Gentleman, Steve M, Parkkinen, Laura, Bertram, Lars, Lill, Christina M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645562/
https://www.ncbi.nlm.nih.gov/pubmed/36382223
http://dx.doi.org/10.1093/braincomms/fcac274
_version_ 1784826988533383168
author Dobricic, Valerija
Schilling, Marcel
Farkas, Ildiko
Gveric, Djordje O
Ohlei, Olena
Schulz, Jessica
Middleton, Lefkos
Gentleman, Steve M
Parkkinen, Laura
Bertram, Lars
Lill, Christina M
author_facet Dobricic, Valerija
Schilling, Marcel
Farkas, Ildiko
Gveric, Djordje O
Ohlei, Olena
Schulz, Jessica
Middleton, Lefkos
Gentleman, Steve M
Parkkinen, Laura
Bertram, Lars
Lill, Christina M
author_sort Dobricic, Valerija
collection PubMed
description Dysregulation of microRNA gene expression has been implicated in many neurodegenerative diseases, including Parkinson’s disease. However, the individual dysregulated microRNAs remain largely unknown. Previous meta-analyses have highlighted several microRNAs being differentially expressed in post-mortem Parkinson’s disease and Alzheimer's disease brains versus controls, but they were based on small sample sizes. In this study, we quantified the expression of the most compelling Parkinson’s and Alzheimer’s disease microRNAs from these meta-analyses (‘candidate miRNAs’) in one of the largest Parkinson’s/Alzheimer’s disease case–control post-mortem brain collections available (n = 451), thereby quadruplicating previously investigated sample sizes. Parkinson’s disease candidate microRNA hsa-miR-132-3p was differentially expressed in our Parkinson’s (P = 4.89E−06) and Alzheimer’s disease samples (P = 3.20E−24) compared with controls. Alzheimer’s disease candidate microRNAs hsa-miR-132-5p (P = 4.52E−06) and hsa-miR-129-5p (P = 0.0379) were differentially expressed in our Parkinson’s disease samples. Combining these novel data with previously published data substantially improved the statistical support (α = 3.85E−03) of the corresponding meta-analyses, clearly implicating these microRNAs in both Parkinson’s and Alzheimer’s disease. Furthermore, hsa-miR-132-3p/-5p (but not hsa-miR-129-5p) showed association with α-synuclein neuropathological Braak staging (P = 3.51E−03/P = 0.0117), suggesting that hsa-miR-132-3p/-5p play a role in α-synuclein aggregation beyond the early disease phase. Our study represents the largest independent assessment of recently highlighted candidate microRNAs in Parkinson’s and Alzheimer’s disease brains, to date. Our results implicate hsa-miR-132-3p/-5p and hsa-miR-129-5p to be differentially expressed in both Parkinson’s and Alzheimer’s disease, pinpointing shared pathogenic mechanisms across these neurodegenerative diseases. Intriguingly, based on publicly available high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation data, hsa-miR-132 may interact with SNCA messenger RNA in the human brain, possibly pinpointing novel therapeutic approaches in fighting Parkinson’s disease.
format Online
Article
Text
id pubmed-9645562
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-96455622022-11-14 Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains Dobricic, Valerija Schilling, Marcel Farkas, Ildiko Gveric, Djordje O Ohlei, Olena Schulz, Jessica Middleton, Lefkos Gentleman, Steve M Parkkinen, Laura Bertram, Lars Lill, Christina M Brain Commun Original Article Dysregulation of microRNA gene expression has been implicated in many neurodegenerative diseases, including Parkinson’s disease. However, the individual dysregulated microRNAs remain largely unknown. Previous meta-analyses have highlighted several microRNAs being differentially expressed in post-mortem Parkinson’s disease and Alzheimer's disease brains versus controls, but they were based on small sample sizes. In this study, we quantified the expression of the most compelling Parkinson’s and Alzheimer’s disease microRNAs from these meta-analyses (‘candidate miRNAs’) in one of the largest Parkinson’s/Alzheimer’s disease case–control post-mortem brain collections available (n = 451), thereby quadruplicating previously investigated sample sizes. Parkinson’s disease candidate microRNA hsa-miR-132-3p was differentially expressed in our Parkinson’s (P = 4.89E−06) and Alzheimer’s disease samples (P = 3.20E−24) compared with controls. Alzheimer’s disease candidate microRNAs hsa-miR-132-5p (P = 4.52E−06) and hsa-miR-129-5p (P = 0.0379) were differentially expressed in our Parkinson’s disease samples. Combining these novel data with previously published data substantially improved the statistical support (α = 3.85E−03) of the corresponding meta-analyses, clearly implicating these microRNAs in both Parkinson’s and Alzheimer’s disease. Furthermore, hsa-miR-132-3p/-5p (but not hsa-miR-129-5p) showed association with α-synuclein neuropathological Braak staging (P = 3.51E−03/P = 0.0117), suggesting that hsa-miR-132-3p/-5p play a role in α-synuclein aggregation beyond the early disease phase. Our study represents the largest independent assessment of recently highlighted candidate microRNAs in Parkinson’s and Alzheimer’s disease brains, to date. Our results implicate hsa-miR-132-3p/-5p and hsa-miR-129-5p to be differentially expressed in both Parkinson’s and Alzheimer’s disease, pinpointing shared pathogenic mechanisms across these neurodegenerative diseases. Intriguingly, based on publicly available high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation data, hsa-miR-132 may interact with SNCA messenger RNA in the human brain, possibly pinpointing novel therapeutic approaches in fighting Parkinson’s disease. Oxford University Press 2022-10-28 /pmc/articles/PMC9645562/ /pubmed/36382223 http://dx.doi.org/10.1093/braincomms/fcac274 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Dobricic, Valerija
Schilling, Marcel
Farkas, Ildiko
Gveric, Djordje O
Ohlei, Olena
Schulz, Jessica
Middleton, Lefkos
Gentleman, Steve M
Parkkinen, Laura
Bertram, Lars
Lill, Christina M
Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title_full Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title_fullStr Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title_full_unstemmed Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title_short Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
title_sort common signatures of differential microrna expression in parkinson’s and alzheimer’s disease brains
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645562/
https://www.ncbi.nlm.nih.gov/pubmed/36382223
http://dx.doi.org/10.1093/braincomms/fcac274
work_keys_str_mv AT dobricicvalerija commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT schillingmarcel commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT farkasildiko commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT gvericdjordjeo commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT ohleiolena commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT schulzjessica commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT middletonlefkos commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT gentlemanstevem commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT parkkinenlaura commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT bertramlars commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains
AT lillchristinam commonsignaturesofdifferentialmicrornaexpressioninparkinsonsandalzheimersdiseasebrains