TY - JOUR
T1 - Downregulation of miR-335-5P in Amyotrophic Lateral Sclerosis Can Contribute to Neuronal Mitochondrial Dysfunction and Apoptosis
AU - De Luna, Noemi
AU - Turon-Sans, Joana
AU - Cortes-Vicente, Elena
AU - Carrasco-Rozas, Ana
AU - Illán-Gala, Ignacio
AU - Dols-Icardo, Oriol
AU - Clarimón, Jordi
AU - Lleó, Alberto
AU - Gallardo, Eduard
AU - Illa, Isabel
AU - Rojas-García, Ricardo
N1 - Funding Information:
The authors thank the patients and their relatives for their support for this study. The study was supported by grants from the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III, Spanish Ministry of Health (PI15/1618 and PI19/01543 to R.R.), and partly jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Union Éuropea, Una manera de hacer Europa. This work was also supported by Fundació La Marató de TV3 (201437.10 to R.R.). I. I-G is supported by the Rio Hortega grant (CM17/00074) from “Acción Estratégica en Salud 2013-2016” and the European Social Fund and the Global Brain Health Institute (Atlantic fellow for equity and brain health at GBHI; https://www.gbhi.org/).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85081605548
U2 - 10.1038/s41598-020-61246-1
DO - 10.1038/s41598-020-61246-1
M3 - Article
C2 - 32152380
AN - SCOPUS:85081605548
SN - 2045-2322
VL - 10
JO - SCIENTIFIC REPORTS
JF - SCIENTIFIC REPORTS
IS - 1
M1 - 4308
ER -