![]() ![]() Given the stability in various body fluids and protection of enclosed RNA from enzymatic degradation, sEV may be a more reliable source of biomarker than free-floating circulating miRNAs 16. Exosome-mediated transfer of miRNA from neuron has been demonstrated to regulate glutamate transporter-1 expression in astrocyte (and thereby extracellular glutamate levels) and phenotypic alterations in microglia 14, 15. Studies have shown that sEV can transfer ALS-associated proteins such as SOD1 and TDP-43 and may induce the prion-like propagation of protein misfolding and aggregates 12, 13. A growing body of evidence has implicated sEV as an important platform for intercellular communication in various physiological and pathological processes 11. Small extracellular vesicles (sEV) such as exosomes and microvesicles are nano-sized (40–100 nm) lipid membrane vesicles released by various cell types which contain bioactive molecules such as nucleic acids and proteins 10. ![]() Notably, however, very few miRNA overlap across different studies, which may reflect biological heterogeneity of the disease, small size of study cohort and methodological differences in sample preparation and miRNA profiling 8. A number of biomarker studies have been undertaken to identify circulating cell-free miRNAs in ALS 9. Emerging evidence suggests that dysregulation of miRNA is implicated in the pathomechanism of ALS 8. MicroRNAs (miRNA) are endogenous small non-coding RNAs (18–23 nucleotides long) which regulate gene expression at post-transcriptional level 7. Therefore, effective biomarkers that can reflect heterogeneity and pathophysiology of ALS may help to expedite diagnosis and better design therapeutic trials 6. The pathogenesis is incompletely understood with more than 40 genes identified as being causative or associated with ALS 4.ĭiagnosis of ALS is a clinically driven exclusion process which often results in considerable diagnostic delay in part due to a wide variability of clinical phenotypes and the lack of reliable biomarkers 5. Most cases are sporadic, while up to 10% of patients have a family history 3. It causes a relentlessly fast-progressing motor neuron loss which leads to generalized skeletal muscle wasting, spasticity and ultimately death due to respiratory failure within 2–5 years after symptom onset 2. Similar content being viewed by othersĪmyotrophic lateral sclerosis (ALS) is a fatal and heterogeneous neurodegenerative disease with no known cure 1. Our results suggest that circulating sEV from ALS patients have distinct miRNA profiles which may be potentially useful as a biomarker of the disease. ![]() ![]() Bioinformatic analysis revealed that these two miRNAs interact with distinct sets of target genes and involve biological processes relevant to the pathomechanism of ALS. Two of them (up- and down-regulation of miR-23c and miR192-5p, respectively) were confirmed in a separate validation cohort (18 patients and 15 healthy controls) by droplet digital PCR. Here, we performed small RNA sequencing analysis of serum sEV and identified 5 differentially expressed miRNA in a discovery cohort of 12 patients and 11 age- and sex-matched healthy controls (fold change > 2, p < 0.05). Although circulating cell-free miRNA have been extensively investigated in ALS, sEV-derived miRNAs have not been systemically explored yet. Dysregulation of microRNAs (miRNA) in small extracellular vesicles (sEV) such as exosomes have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). ![]()
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