MiR-146a in ALS: Contribution to Early Peripheral Nerve Degeneration and Relevance as Disease Biomarker

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4610
• Main Authors: Giagnorio, Eleonora, Malacarne, Claudia, Cavalcante, Paola, Scandiffio, Letizia, Cattaneo, Marco, Pensato, Viviana, Gellera, Cinzia, Riva, Nilo, Quattrini, Angelo, Dalla Bella, Eleonora, Lauria, Giuseppe, Mantegazza, Renato, Bonanno, Silvia, Marcuzzo, Stefania
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.02.2023; MDPI
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Animals; axon degeneration; Axons - pathology; biomarker; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Body fluids; Degeneration; Development and progression; Disease; Disease Models, Animal; Disease Progression; Early Diagnosis; Gene expression; Genes; Humans; Hybridization; Metabolism; Mice; Mice, Transgenic; MicroRNA; microRNA-146a; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular modelling; Motor neurons; Nerve Degeneration - diagnosis; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Nervous system; Neurofilament Proteins; Neuromuscular diseases; Neurophysiology; Pathogenesis; Peripheral nerves; Peripheral Nerves - pathology; Pharmaceutical industry; Physiological aspects; Proteins; Sciatic nerve; Scientific equipment and supplies industry; Spinal cord; Superoxide dismutase; Superoxide Dismutase-1 - genetics; United States; microRNA-146a; biomarker; amyotrophic lateral sclerosis; axon degeneration
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054610

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive, irreversible loss of upper and lower motor neurons (UMNs, LMNs). MN axonal dysfunctions are emerging as relevant pathogenic events since the early ALS stages. However, the exact molecular mechanisms leading to MN axon degeneration in ALS still need to be clarified. MicroRNA (miRNA) dysregulation plays a critical role in the pathogenesis of neuromuscular diseases. These molecules represent promising biomarkers for these conditions since their expression in body fluids consistently reflects distinct pathophysiological states. Mir-146a has been reported to modulate the expression of the NFL gene, encoding the light chain of the neurofilament (NFL) protein, a recognized biomarker for ALS. Here, we analyzed miR-146a and expression in the sciatic nerve of G93A-SOD1 ALS mice during disease progression. The miRNA was also analyzed in the serum of affected mice and human patients, the last stratified relying on the predominant UMN or LMN clinical signs. We revealed a significant miR-146a increase and expression decrease in G93A-SOD1 peripheral nerve. In the serum of both ALS mice and human patients, the miRNA levels were reduced, discriminating UMN-predominant patients from the LMN ones. Our findings suggest a miR-146a contribution to peripheral axon impairment and its potential role as a diagnostic and prognostic biomarker for ALS.