Aim: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the progressive degeneration of motor neurons. MicroRNAs are 17 - 27 nucleotide long molecules that regulate post-transcriptional mRNA expression. The aim of this study was to investigate the role of microRNAs in the skeletal muscle of ALS patients and correlate these results with the expression of histone deacetylase 4 (HDAC4) protein.
Materials and methods: We measured the expression levels of muscle-specific microRNAs (miR-1, miR-133a, miR-133b, miR-206), inflammatory micro-RNAs (miR-27a, miR-221, miR-155), and HDAC4 protein content on western blotting in muscle biopsies obtained for diagnostic reasons in 18 ALS patients: 8 genetic forms (C9-ALS and SOD1-ALS), 5 sporadic cases (SALS), and 5 ALS cases affected only by upper motor neuron disease (UMN).
Results: In muscle of patients with genetic forms of ALS, we found a strong upregulation of miR-206, a muscle-specific miRNA involved in neuromuscular junction (NMJ), regeneration and muscle atrophy, and a decreased expression of HDAC4 protein levels, which is involved both in denervation and regulation of miR-206 in ALS pathophysiology. In these patients, we also observed an increase of inflammatory miRNAs.
Conclusion: The different expression of miRNAs and HDAC4 in genetic ALS vs. SALS and UMN cases is likely to be correlated to different pathogenic mechanisms.