TY - JOUR
T1 - Dysregulation of muscle-specific micrornas as common pathogenic feature associated with muscle atrophy in als, sma and sbma
T2 - Evidence from animal models and human patients
AU - Malacarne, Claudia
AU - Galbiati, Mariarita
AU - Giagnorio, Eleonora
AU - Cavalcante, Paola
AU - Salerno, Franco
AU - Andreetta, Francesca
AU - Cagnoli, Cinza
AU - Taiana, Michela
AU - Nizzardo, Monica
AU - Corti, Stefania
AU - Pensato, Viviana
AU - Venerando, Anna
AU - Gellera, Cinzia
AU - Fenu, Silvia
AU - Pareyson, Davide
AU - Masson, Riccardo
AU - Maggi, Lorenzo
AU - Bella, Eleonora Dalla
AU - Lauria, Giuseppe
AU - Mantegazza, Renato
AU - Bernasconi, Pia
AU - Poletti, Angelo
AU - Bonanno, Silvia
AU - Marcuzzo, Stefania
N1 - Funding Information:
Funding: This research was funded by the Italian Ministry of Health, years 2015–2020 (R.M., S.M., annual research funding), the Fondazione Regionale per la Ricerca Biomedica (FRRB; TRANS-ALS, Grant No. 2015-0023 to G.L.), Cariplo (Grant No. 2017-1886 to S.B.), Fondazione Telethon, Italy (Grant No. GGP14039 and GGP19128 to A.P.), Fondazione ARISLA, Italy (n. ALS_HSPB8 to A.P.; ALS_Granulopathy to A.P.; MLOpathy to A.P.; Target-RAN to A.P.), PRIN-Progetti di ricerca di interesse nazionale (n. 2015LFPNMN to A.P.; n. 2017F2A2C5 to A.P.), Bando Straordinario per Progetti Interdipartimentali (Bando SEED 2019, Gender-ALS to M.G.), Kennedy’s Disease Association (2020 granto to M.G.), and the Italian Ministry of University and Research [Progetto Dipartimenti di Eccellenza].
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Motor neuron diseases
KW - Mouse models
KW - Muscle-specific microRNAs
KW - Spinal bulbar muscular atrophy
KW - Spinal muscular atrophy
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U2 - 10.3390/ijms22115673
DO - 10.3390/ijms22115673
M3 - Article
AN - SCOPUS:85106398378
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
M1 - 5673
ER -