Tags

Type your tag names separated by a space and hit enter

Common signatures of differential microRNA expression in Parkinson's and Alzheimer's disease brains.
Brain Commun. 2022; 4(6):fcac274.BC

Abstract

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.

Authors+Show Affiliations

Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany.Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany.Multiple Sclerosis and Parkinson's Tissue Bank, Imperial College London, London W12 0NN, UK.Multiple Sclerosis and Parkinson's Tissue Bank, Imperial College London, London W12 0NN, UK.Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany.Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany.Ageing and Epidemiology Unit (AGE), School of Public Health, Imperial College London, London W6 8RF, UK. Public Health Directorate, Imperial College NHS Healthcare Trust, London W6 8RF, UK.Department of Brain Sciences, Hammersmith Hospital campus, Imperial College London, London W12 0HS, UK.Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX3 9DU, UK.Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany. Department of Psychology, University of Oslo, 0373 Oslo, Norway.Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany. Ageing and Epidemiology Unit (AGE), School of Public Health, Imperial College London, London W6 8RF, UK. Institute of Epidemiology and Social Medicine, University of Münster, 48149 Münster, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36382223

Citation

Dobricic, Valerija, et al. "Common Signatures of Differential microRNA Expression in Parkinson's and Alzheimer's Disease Brains." Brain Communications, vol. 4, no. 6, 2022, pp. fcac274.
Dobricic V, Schilling M, Farkas I, et al. Common signatures of differential microRNA expression in Parkinson's and Alzheimer's disease brains. Brain Commun. 2022;4(6):fcac274.
Dobricic, V., Schilling, M., Farkas, I., Gveric, D. O., Ohlei, O., Schulz, J., Middleton, L., Gentleman, S. M., Parkkinen, L., Bertram, L., & Lill, C. M. (2022). Common signatures of differential microRNA expression in Parkinson's and Alzheimer's disease brains. Brain Communications, 4(6), fcac274. https://doi.org/10.1093/braincomms/fcac274
Dobricic V, et al. Common Signatures of Differential microRNA Expression in Parkinson's and Alzheimer's Disease Brains. Brain Commun. 2022;4(6):fcac274. PubMed PMID: 36382223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Common signatures of differential microRNA expression in Parkinson's and Alzheimer's disease brains. AU - Dobricic,Valerija, AU - Schilling,Marcel, AU - Farkas,Ildiko, AU - Gveric,Djordje O, AU - Ohlei,Olena, AU - Schulz,Jessica, AU - Middleton,Lefkos, AU - Gentleman,Steve M, AU - Parkkinen,Laura, AU - Bertram,Lars, AU - Lill,Christina M, Y1 - 2022/10/28/ PY - 2022/04/07/received PY - 2022/06/22/revised PY - 2022/10/26/accepted PY - 2022/11/16/entrez PY - 2022/11/17/pubmed PY - 2022/11/17/medline KW - Alzheimer’s disease KW - Parkinson’s disease KW - brain KW - expression KW - miRNA SP - fcac274 EP - fcac274 JF - Brain communications JO - Brain Commun VL - 4 IS - 6 N2 - 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. SN - 2632-1297 UR - https://www.unboundmedicine.com/medline/citation/36382223/Common_signatures_of_differential_microRNA_expression_in_Parkinson's_and_Alzheimer's_disease_brains_ DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.