MyomiRNAs Dysregulation in ALS Rehabilitation.

Valentina Pegoraro,Antonio Merico,Corrado Angelini

doi:10.3390/brainsci9010008

Valentina Pegoraro, Antonio Merico + Show 1 more

Open Access

https://doi.org/10.3390/brainsci9010008

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Journal: Brain sciences	Publication Date: Jan 10, 2019
Citations: 26	License type: CC BY 4.0

Affiliation: Ospedale generale di zona San Camillo Treviso

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disorder caused by degeneration of upper and lower motor neurons. The disease process leads, because of lower motor neuron involvement, to progressive muscle atrophy, weakness, and fasciculations and for the upper motor neuron involvement leads to spasticity. Muscle atrophy in ALS is caused by a neural dysregulation in the molecular network controlling fast and slow muscle fibers. Denervation and reinnervation processes in skeletal muscle occur in the course of ALS and are modulated by rehabilitation. MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in different biological functions under various pathophysiological conditions. MiRNAs can be secreted by various cell types and they are markedly stable in body fluids. MiR-1, miR-133 a miR-133b, and miR-206 are called “myomiRs” and are considered markers of myogenesis during muscle regeneration and contribute to neuromuscular junction stabilization or sprouting. We observed a positive effect of a standard aerobic exercise rehabilitative protocol conducted for six weeks in 18 ALS patients during hospitalization in our center. This is a preliminary study, in which we correlated clinical scales with molecular data on myomiRs. After six weeks of moderate aerobic exercise, we found lower levels in serum of myomiRNAs. Our data suggest that circulating miRNAs changed during skeletal muscle recovery in response to physical rehabilitation in ALS. However, no firm conclusions can be made on the ALS-specific effect of exercise on miRNA levels.

Highlights

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disease that involves both lower motor neurons in the spinal cord or brainstem and upper motor neurons
We found that regular, rehabilitative exercise in ALS patients helped to reduce pain and fatigue of skeletal muscle origin [12]
We propose that the decrease in levels of myomiRs that we found after training stabilization of skeletal muscle and muscle neuromuscular junction (NMJ)

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disease that involves both lower motor neurons in the spinal cord or brainstem and upper motor neurons. Two-thirds of patients with ALS have the classical ‘spinal form’ of the disease [2], with onset in lower limbs and symptoms associated with muscle atrophy. Patients with a bulbar onset of ALS initially exhibit dysarthria and dysphagia for solids and liquids [2]. In ALS, death occurs within 3–5 years but there is great variability in the duration of the disease, since some patients die a few months after the onset and others survive for more than twenty years [1]. Pathogenic processes leading to the disease involve both motor-neurons and non-neuronal cells, including astrocytes, microglia, T-cells, and skeletal muscle. Muscle atrophy in ALS is caused by a dysregulation in the “molecular network”

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