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

International Journal of Molecular Sciences

Riccardo Masson¹  Michela Taiana²  Stefania Corti²  Angelo Poletti³  Mariarita Galbiati³  Cinza Cagnoli⁴  Giuseppe Lauria⁵  Eleonora Dalla Bella⁵  Paola Cavalcante⁶  Franco Salerno⁶  Claudia Malacarne⁶  Lorenzo Maggi⁶  Silvia Bonanno⁶  Pia Bernasconi⁶  Francesca Andreetta⁶  Renato Mantegazza⁶  Stefania Marcuzzo⁶  Eleonora Giagnorio⁶  Monica Nizzardo⁷  Viviana Pensato⁸  Anna Venerando⁸  Cinzia Gellera⁸  Silvia Fenu⁹  Davide Pareyson⁹ 

[1] Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy;Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Via Balzaretti, 9, 20133 Milano, Italy;Molecular Neuroanatomy and Pathogenesis Unit, Neurology VII—Clinical and Experimental Epileptology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;Neurology IV–Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;Neurology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy;Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;Unit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy;

关键词: motor neuron diseases;    muscle-specific microRNAs;    amyotrophic lateral sclerosis;    spinal muscular atrophy;    spinal bulbar muscular atrophy;    mouse models;   

DOI  :  10.3390/ijms22115673

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown