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 MalacarneMariarita GalbiatiEleonora GiagnorioPaola CavalcanteFranco SalernoFrancesca AndreettaCinzia CagnoliMichela TaianaMonica NizzardoStefania CortiViviana PensatoAnna VenerandoCinzia GelleraSilvia FenuDavide PareysonRiccardo MassonLorenzo MaggiEleonora Dalla BellaGiuseppe LauriaRenato MantegazzaPia BernasconiAngelo PolettiSilvia BonannoStefania MarcuzzoPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- skeletal muscle
- amyotrophic lateral sclerosis
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- machine learning
- spinal cord
- squamous cell carcinoma
- long noncoding rna
- radiation therapy
- adipose tissue
- mass spectrometry
- transcription factor
- real time pcr
- spinal cord injury
- binding protein
- artificial intelligence
- combination therapy
- human health