Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS, SMA and SBMA: Evidence from Animal Models and Human Patients.

Abstract

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients' sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.

• Authors: Claudia Malacarne, Mariarita Galbiati, Eleonora Giagnorio, Paola Cavalcante, Franco Salerno, Francesca Andreetta, Cinza Cagnoli, Michela Taiana, Monica Nizzardo, Stefania Corti, Viviana Pensato, Anna Venerando, Cinzia Gellera, Silvia Fenu, Davide Pareyson, Riccardo Masson, Lorenzo Maggi, Eleonora Dalla Bella, Giuseppe Lauria, Renato Mantegazza, Pia Bernasconi, Angelo Poletti, Silvia Bonanno, Stefania Marcuzzo
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 11 (May 26 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34073630 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• SOD1 protein, human
• SOD1 G93A protein
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Amino Acid Substitution
• Amyotrophic Lateral Sclerosis (genetics, metabolism)
• Animals
• Bulbo-Spinal Atrophy, X-Linked (genetics, metabolism)
• Humans
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Mutation, Missense
• Superoxide Dismutase (genetics, metabolism)
• Superoxide Dismutase-1 (genetics, metabolism)