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Identification of a circulating miRNA signature in extracellular vesicles collected from amyotrophic lateral sclerosis patients
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with the progressive death of motor neurons. Mean survival for a patient diagnosed with ALS is between 2 and 5 years. Early and efficient diagnosis of the various forms of ALS remains a significant challenge, resulting in a need to identify clinically-relevant biomarkers in readily accessible body fluids. microRNAs (miRNAs) are short, evolutionarily conserved non-coding RNA molecules involved in post-transcriptional regulation of gene expression that have received interest as disease biomarkers. This study was undertaken to identify an ALS-associated miRNA signature in extracellular vesicles (EVs), which can cross the blood-brain barrier and enter the circulatory system, obtained from plasma samples of persons diagnosed and living with ALS (PALS). Next-generation sequencing was used to identify differentially expressed miRNAs recovered from EVs of PALS and healthy controls. High-throughput sequencing data for select miRNA targets was subsequently validated by droplet digital PCR (ddPCR). This approach revealed elevated levels of 5 miRNAs and reduced levels of 22 miRNAs in EVs collected from PALS as compared with healthy controls subjects. miRNAs with relevance to ALS were found to be deregulated, including miR-9-5p, miR-183-5p, miR-338-3p and miR-1246. MiR-15a-5p and miR-193a-5p were identified for their diagnostic potential of ALS and association with disability progression, respectively. Function…
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“Dysregulation of microRNA (miRNA) expression in the brain is a common feature of neurodegenerative diseases.”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [14]
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Xu, X., Iqbal, Z., Xu, L., Wen, C., Duan, L., Xia, J., Yang, N., Zhang, Y., & Liang, Y. (2024) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13610 · Cited by 68
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Metadata
- Authors
- Saucier, D., Wajnberg, G., Roy, J., Beauregard, A.-P., Chacko, S., Crapoulet, N., Fournier, S., Ghosh, A., Lewis, S. M., Marrero, A., O'Connell, C., Ouellette, R. J., & Morin, P. J.
- ORCID
- Wajnberg, Gabriel
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 1708
- Pages
- 100-108
- ISSN
- 0006-8993
- Cited by
- 119
- References
- 6
- Language
- en
- Funders
- ALS Canada
- Brain Canada
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