Serum microRNAs in sporadic amyotrophic lateral sclerosis

Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial a...

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Veröffentlicht in:Neurobiology of aging 2015-09, Vol.36 (9), p.2660.e15-2660.e20
Hauptverfasser: Freischmidt, Axel, Müller, Kathrin, Zondler, Lisa, Weydt, Patrick, Mayer, Benjamin, von Arnim, Christine A.F, Hübers, Annemarie, Dorst, Johannes, Otto, Markus, Holzmann, Karlheinz, Ludolph, Albert C, Danzer, Karin M, Weishaupt, Jochen H
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container_end_page 2660.e20
container_issue 9
container_start_page 2660.e15
container_title Neurobiology of aging
container_volume 36
creator Freischmidt, Axel
Müller, Kathrin
Zondler, Lisa
Weydt, Patrick
Mayer, Benjamin
von Arnim, Christine A.F
Hübers, Annemarie
Dorst, Johannes
Otto, Markus
Holzmann, Karlheinz
Ludolph, Albert C
Danzer, Karin M
Weishaupt, Jochen H
description Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments.
doi_str_mv 10.1016/j.neurobiolaging.2015.06.003
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Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. 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subjects Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - blood
Amyotrophic Lateral Sclerosis - genetics
Biomarker
Cluster Analysis
Cohort Studies
Computational Biology
Diagnosis
Down-Regulation
Female
Gene Expression Regulation
Humans
Internal Medicine
Male
Microarray Analysis
MicroRNA
MicroRNAs - blood
MicroRNAs - genetics
Mutation
Neurology
RNA, Messenger - metabolism
Serum
title Serum microRNAs in sporadic amyotrophic lateral sclerosis
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