MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease with a wide disease progression. Despite several efforts to develop efficient biomarkers, many concerns about the available ones still need to be addressed. MicroRNA (miR) are non-coding RNAs that can modulate molecular circuits and are involved in ALS pathogenic mechanisms.

Wheel Running Adversely Affects Disease Onset and Neuromuscular Interplay in Amyotrophic Lateral Sclerosis Slow Progression Mouse Model.

Background: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial role. In some epidemiological studies, both recreational or professional sport exercise has been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise have not been fully elucidated in either patients or animal models.

Methods: To better reproduce the influence of this environmental factor in the pathogenesis of ALS, we exposed SOD1 low-copy male mice to multiple exercise sessions at asymptomatic and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3 months.

Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis.

The anatomical substrate of skeletal muscle autonomic innervation has remained underappreciated since it was described many decades ago. As such, the structural and functional features of muscle sympathetic innervation are largely undetermined in both physiology and pathology, mainly due to methodological limitations in the histopathological analysis of small neuronal fibers in tissue samples. Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease which mainly targets motor neurons, and despite autonomic symptoms occurring in a significant fraction of patients, peripheral sympathetic neurons (SNs) are generally considered unaffected and, as such, poorly studied.

Development of a Novel Technique for the Measurement of Neuromuscular Junction Functionality in Isotonic Conditions.

Introduction: The neuromuscular junction (NMJ) is a chemical synapse responsible for converting electrical pulses generated by the motor neuron into electrical activity in muscle fibers, and is severely impaired in various diseases, such as Amyotrophic Lateral Sclerosis (ALS). Here, we proposed a novel technique to measure, for the first time, NMJ functionality in isotonic conditions, which better reflect muscle physiological activity.

Methods: We employed the testing technique, studied a proper placing of two pairs of wire electrodes for nerve and muscle stimulation, developed an extensive testing protocol, and proposed a novel parameter, the Isotonic Neurotransmission Failure (INF), to properly capture the impairments in neurotransmission during isotonic fatigue.

Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition.

ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factors for ALS. MyomiRs are microRNAs produced by skeletal muscle, and they play an important role in tissue homeostasis; moreover, they can be released in blood circulation in pathological conditions, including ALS.

Fenretinide Beneficial Effects on Amyotrophic Lateral Sclerosis-associated SOD1 Mutant Protein Toxicity: In Vitro and In Vivo Evidences.

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease for which effective treatment options are still lacking. ALS occurs in sporadic and familial forms which are clinically indistinguishable; about 20% of familial ALS cases are linked to mutations of the superoxide dismutase 1 (SOD1) gene. Fenretinide (FEN), a cancer chemopreventive and antiproliferative agent currently used in several clinical trials, is a multi-target drug which also exhibits redox regulation activities.

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. To date, multiple panels of biomarkers have been described in ALS patients and murine models. Nevertheless, none of them has sufficient specificity and thus the molecular signature for ALS prognosis and progression remains to be elucidated.

Neuromuscular Junction as an Entity of Nerve-Muscle Communication.

One of the crucial systems severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. The neuromuscular junction (NMJ) represents the critical region at the level of which muscle and nerve communicate. Defects in signal transmission between terminal nerve endings and muscle membrane is a common feature of several physio-pathologic conditions including aging and Amyotrophic Lateral Sclerosis (ALS).