Downregulation of miR-335-5P in Amyotrophic Lateral Sclerosis Can Contribute to Neuronal Mitochondrial Dysfunction and Apoptosis.

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

De Luna N,Turon-Sans J,Cortes-Vicente E,Carrasco-Rozas A,Illán-Gala I,Dols-Icardo O,Clarimón J,Lleó A,Gallardo E,Illa I,Rojas-García R

doi

10.1038/s41598-020-61246-1

subject

Has Abstract

pub_date

2020-03-09 00:00:00

pages

4308

issue

1

issn

2045-2322

pii

10.1038/s41598-020-61246-1

journal_volume

10

pub_type

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