Skeletal Muscle Satellite Cells in Amyotrophic Lateral Sclerosis

Scaramozza, Annarita; Marchese, Valeria; Papa, Valentina; Salaroli, Roberta; Sorarù, Gian Domenico; Angelini, C.; Cenacchi, Giovanna

doi:10.3109/01913123.2014.937842

Cited by 52 publications

(60 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most importantly, satellite cells isolated from presymptomatic animals exhibited less proliferative capacity in vitro than satellite cells isolated from wild-type littermates (73). This diminished capacity to develop normally was also observed in satellite cells derived from ALS patients (94,103). As these cells neither contract nor receive direct motor neuronal input, it is speculated that their modifications could attest at least in part to an intrinsic muscle pathology.…”

Section: Motor Neurons or Myofibers: Who Are First?mentioning

confidence: 96%

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

et al. 2016

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets.

show abstract

Section: Motor Neurons or Myofibers: Who Are First?mentioning

confidence: 96%

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…; Scaramozza et al. ). However, whether skeletal muscle satellite cell differentiation is affected by spinal cord injury in humans remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…; Scaramozza et al. ). Thus, primary human skeletal muscle cultures have provided meaningful insight into satellite cell function in muscle disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Denervation of rat skeletal muscle leads to formation of new myotubes with defective contractile machinery (Carraro et al 2015). Skeletal muscle satellite cells from individuals with amyotrophic lateral sclerosis have reduced differentiation capacity and form myotubes with abnormal morphology (Pradat et al 2011;Scaramozza et al 2014). However, whether skeletal muscle satellite cell differentiation is affected by spinal cord injury in humans remains unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals

et al. 2018

View full text Add to dashboard Cite

Despite the well‐known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord‐injured and six able‐bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer‐based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able‐bodied and spinal cord‐injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord‐injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord‐injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt‐mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord‐injured individuals was unchanged (P > 0.05) compared to able‐bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy.

show abstract

“…Previous studies have shown that the exclusive expression of mutant SOD1G93A (mSOD1) in the skeletal muscles can lead to denervation of the neuromuscular junctions (NMJs), which lose the ability to regenerate and become atrophic, thus contributing to the symptoms of ALS . Indeed, several mechanisms implicated in the physiological maintenance of skeletal muscle are deregulated in ALS, such as satellite cell (SC) activity, mitochondrial and miRNA biogenesis . It is interesting that these processes act synergistically to maintain healthy skeletal muscle, and influence both the number and the activity of the innervated junctions .…”

Section: Introductionmentioning

confidence: 99%

P2X7 activation enhances skeletal muscle metabolism and regeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis

et al. 2019

View full text Add to dashboard Cite

Muscle weakness plays an important role in neuromuscular disorders comprising amyotrophic lateral sclerosis (ALS). However, it is not established whether muscle denervation originates from the motor neurons, the muscles or more likely both. Previous studies have shown that the expression of the SOD1G93A mutation in skeletal muscles causes denervation of the neuromuscular junctions, inability to regenerate and consequent atrophy, all clear symptoms of ALS. In this work, we used SOD1G93A mice, a model that best mimics some pathological features of both familial and sporadic ALS, and we investigated some biological effects induced by the activation of the P2X7 receptor in the skeletal muscles. The P2X7, belonging to the ionotropic family of purinergic receptors for extracellular ATP, is abundantly expressed in the healthy skeletal muscles, where it controls cell duplication, differentiation, regeneration or death. In particular, we evaluated whether an in vivo treatment in SOD1G93A mice with the P2X7 specific agonist 2′(3′)‐O‐(4‐Benzoylbenzoyl) adenosine5′‐triphosphate (BzATP) just before the onset of a pathological neuromuscular phenotype could exert beneficial effects in the skeletal muscles. Our findings indicate that stimulation of P2X7 improves the innervation and metabolism of myofibers, moreover elicits the proliferation/differentiation of satellite cells, thus preventing the denervation atrophy of skeletal muscles in SOD1G93A mice. Overall, this study suggests that a P2X7‐targeted and site‐specific modulation might be a strategy to interfere with the complex multifactorial and multisystem nature of ALS.

show abstract

Skeletal Muscle Satellite Cells in Amyotrophic Lateral Sclerosis

Abstract: Our data suggest that the capacity of ALS SCs to proceed through the myogenic program seems to be altered: SCs seem to lose their ability to regenerate and restore mature myofibers.

Cited by 52 publications

References 17 publications

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals

P2X7 activation enhances skeletal muscle metabolism and regeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis

Contact Info

Product

Resources

About