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Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease for which the pathophysiological mechanisms of motor neuron loss are not precisely clarified. Environmental and epigenetic mechanisms such as microRNAs (miRNAs) could have a role in disease progression. We studied the expression pattern of miRNAs in ALS serum from 60 patients and 29 healthy controls. We also analyzed how deregulated miRNAs found in serum affected cellular pathways such as apoptosis, autophagy and mitochondrial physiology in SH-SY5Y cells. We found that miR-335-5p was downregulated in ALS serum. SH-SY5Y cells were transfected with a specific inhibitor of miR-335-5p and showed abnormal mitochondrial morphology, with an increment of reactive species of oxygen and superoxide dismutase activity. Pro-apoptotic caspases-3 and 7 also showed an increased activity in transfected cells. The downregulation of miR-335-5p, which has an effect on mitophagy, autophagy and apoptosis in SH-SY5Y neuronal cells could have a role in the motor neuron loss observed in ALS.
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1 Universitat Autónoma de Barcelona, Neuromuscular Diseases Laboratory - Biomedical Research Institute SantPau, Barcelona, Spain (GRID:grid.7080.f); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain (GRID:grid.452372.5) (ISNI:0000 0004 1791 1185)
2 Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Department of Neurology, Barcelona, Spain (GRID:grid.452372.5); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain (GRID:grid.452372.5) (ISNI:0000 0004 1791 1185)
3 Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Sant Pau Memory Unit, Department of Neurology, Barcelona, Spain (GRID:grid.452372.5); Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Valencia, Spain (GRID:grid.452372.5)
4 Universitat Autónoma de Barcelona, Neuromuscular Diseases Laboratory - Biomedical Research Institute SantPau, Barcelona, Spain (GRID:grid.7080.f); Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Department of Neurology, Barcelona, Spain (GRID:grid.7080.f); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain (GRID:grid.452372.5) (ISNI:0000 0004 1791 1185)