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

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 MantegazzaPia Bernasconi, Angelo Poletti, Silvia Bonanno, Stefania Marcuzzo

Research output: Contribution to journalArticlepeer-review

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, ∆7SMA, 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.

Original languageEnglish
Article number5673
JournalInternational Journal of Molecular Sciences
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 1 2021

Keywords

  • Amyotrophic lateral sclerosis
  • Motor neuron diseases
  • Mouse models
  • Muscle-specific microRNAs
  • Spinal bulbar muscular atrophy
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this