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Published on: August 10, 2018
Serum microRNAs in sporadic amyotrophic lateral sclerosis
Axel Freischmidt1, Kathrin Müller1, Lisa Zondler1
1Department of Neurology, Ulm University, Ulm, Germany.
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.
Insights
Researchers studied circulating microRNAs (miRNAs) in sporadic amyotrophic lateral sclerosis (ALS). While signatures were diverse, some patients showed familial ALS patterns, suggesting genetic links in sporadic ALS.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- MicroRNAs (miRNAs) are key post-transcriptional gene regulators.
- Distinct miRNA profiles are associated with various disease states.
- Previous studies found homogeneous circulating miRNA signatures in familial ALS.
Purpose of the Study:
- To characterize circulating miRNA signatures in sporadic amyotrophic lateral sclerosis (ALS) patients.
- To investigate potential overlaps and differences in miRNA profiles between familial and sporadic ALS.
- To explore the contribution of genetic factors to sporadic ALS etiology.
Main Methods:
- Serum samples from sporadic ALS patients were analyzed for circulating miRNA expression.
- miRNA signatures were compared to those of familial ALS patients and presymptomatic mutation carriers.
- Bioinformatic analyses were employed to identify common and distinct miRNA patterns.
Main Results:
- Sporadic ALS patients exhibited highly heterogeneous circulating miRNA signatures, unlike familial ALS.
- Two specific miRNAs, miR-1234-3p and miR-1825, were consistently downregulated in sporadic ALS.
- A significant subgroup (61%) of sporadic ALS patients displayed miRNA fingerprints similar to familial ALS cases.
Conclusions:
- Genetic factors may play a larger role in sporadic ALS than previously assumed.
- Sporadic ALS presents a more molecularly heterogeneous etiology compared to monogenic forms.
- These findings have implications for developing targeted, disease-modifying treatments for ALS.
