Background and Aims:

Motor neuron diseases (MNDs), including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA), are a heterogeneous group of neurodegenerative disorders characterized by motor neuron loss. Despite variability in onset, progression and genetic causes, these disorders share a common involvement of skeletal muscle that is suspected to have a relevant role in MND pathogenesis.

Due to the key role of muscle-specific microRNAs (myomiRs) in muscle development, here we investigated the expression of miR-206, miR-133a, miR-133b and miR-1 myomiRs, and their target genes, in G93A-SOD1 ALS, Δ7SMA and KI-SBMA mouse muscle during disease progression.

Methods:

MyomiRs and their putative target genes, PAX7, MYOD, MYOG, and MEF2, were analyzed by qPCR in ALS-G93A-SOD1, Δ7SMA-SMA and AR113Q-SBMA mice during disease progression. Sperman’s correlation analyses were performed to examine the myomiR/mRNA relationships. The corresponding myomiR target proteins were analysed by western blot. By qPCR, myomiRs were assessed in serum of 14 ALS-SOD1, 23 SMA pediatric, 10 SBMA patients, and 30 controls, including 19 pediatric patients with encephalitis.

Results:

We revealed myomiRs/mRNA target gene dysregulation as common pathogenic feature of the three MNDs. A similar myomiR signature was observed in serum from SOD1-mutated ALS, SMA and SBMA patients, with miR-206 up-regulation being identified in both animal muscle tissues and patients’sera.

Conclusions:

Our findings highlight the role of myomiRs as contributing factors and promising non-invasive biomarkers in ALS, SMA and SBMA, laying the groundwork for further investigations to explore myomiR potential as future therapeutic targets for MNDs.