Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor neuron degeneration, leading to muscle weakness and paralysis, with no effective treatments available. Early diagnosis could slow disease progression and optimize treatment. MicroRNAs (miRNAs) are being investigated as potential biomarkers due to their regulatory roles in cellular processes and stability in biofluids. However, variability across studies complicates their diagnostic utility in ALS. This study aims to identify significantly dysregulated miRNAs in ALS through meta-analysis to elucidate disease mechanisms and improve diagnostic strategies.

Methods: We systematically searched PubMed, Google Scholar, and the Cochrane Library, following predefined inclusion and exclusion criteria. The primary effect measure was the standardized mean difference (SMD) with a 95% confidence interval, analyzed using a random-effects model. Additionally, we used network pharmacology to examine the targets of dysregulated miRNAs and their roles in ALS pathology.

Results: Analysing 34 studies, we found significant upregulation of hsa-miR-206, hsa-miR-133b, hsa-miR-23a, and hsa-miR-338-3p, and significant downregulation of hsa-miR-218, hsa-miR-21-5p, and hsa-let-7b-5p in ALS patients. These miRNAs are involved in ALS pathophysiology, including stress granule formation, nuclear pore complex, SMCR8 and Sig1R dysfunction, histone methyltransferase complex alterations, and MAPK signaling perturbation, highlighting their critical role in ALS progression.

Conclusion: This study identifies several dysregulated miRNAs in ALS patients, offering insights into their role in the disease and potential as diagnostic biomarkers. These findings enhance our understanding of ALS mechanisms and may inform future diagnostic strategies. Validating these results and exploring miRNA-based interventions are crucial for improving ALS diagnosis and treatment outcomes.