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

Scientific Reports
Noemi De LunaRicardo Rojas-García

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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Citations

Aug 23, 2020·International Journal of Molecular Sciences·Mariano CatanesiAnnamaria Cimini
Nov 17, 2020·Frontiers in Neuroscience·Giovanna MorelloSebastiano Cavallaro
Feb 28, 2021·Mitochondrion·Rishabh JhanjiSimona Bungau
Jul 3, 2021·Frontiers in Cell and Developmental Biology·Sara R OliveiraCecília M P Rodrigues
Sep 3, 2021·Neuroscience and Biobehavioral Reviews·Megan E HuibregtseKeisuke Kawata

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Methods Mentioned

BETA
transfection
PCR

Key Resources (RRID) Mentioned

Addgene_56018
AB_2196009
AB_143165
AB_10722709
AB_2068163
AB_476744
AB_621841
AB_621842

Software Mentioned

Excel
Anaxomics
Applied
Gene
GraphPad Prism
Gene Globe
Biosystems SDS
Zeiss Zen
Globe Data Analysis Center
SPSS Statistics

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