Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.

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Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?

Cells ◽

10.3390/cells10061449 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1449

Author(s):

Cyril Quessada ◽

Alexandra Bouscary ◽

Frédérique René ◽

Cristiana Valle ◽

Alberto Ferri ◽

...

Keyword(s):

Skeletal Muscle ◽

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Motor Neurons ◽

Muscle Metabolism ◽

The Body ◽

Energy Deficit ◽

Acid Oxidation ◽

Progression Of Disease ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons, amyotrophy and skeletal muscle paralysis usually leading to death due to respiratory failure. While generally considered an intrinsic motor neuron disease, data obtained in recent years, including our own, suggest that motor neuron protection is not sufficient to counter the disease. The dismantling of the neuromuscular junction is closely linked to chronic energy deficit found throughout the body. Metabolic (hypermetabolism and dyslipidemia) and mitochondrial alterations described in patients and murine models of ALS are associated with the development and progression of disease pathology and they appear long before motor neurons die. It is clear that these metabolic changes participate in the pathology of the disease. In this review, we summarize these changes seen throughout the course of the disease, and the subsequent impact of glucose–fatty acid oxidation imbalance on disease progression. We also highlight studies that show that correcting this loss of metabolic flexibility should now be considered a major goal for the treatment of ALS.

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TDP-43 in skeletal muscle of patients affected with amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis ◽

10.3109/17482960902810890 ◽

2010 ◽

Vol 11 (1-2) ◽

pp. 240-243 ◽

Cited By ~ 8

Author(s):

Gianni Sorarú ◽

Valeria Orsetti ◽

Emanuele Buratti ◽

Francisco Baralle ◽

Valentina Cima ◽

...

Keyword(s):

Skeletal Muscle ◽

Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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AN AYURVEDIC CASE REPORT ON AMYOTROPHIC LATERAL SCLEROSIS

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj4409112021 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2903-2908

Author(s):

Ambika. K ◽

Arundhathi. K ◽

Lekshmi G. Krishna

Keyword(s):

Quality Of Life ◽

Skeletal Muscle ◽

Amyotrophic Lateral Sclerosis ◽

Case Report ◽

Lower Limbs ◽

Skeletal Muscle Weakness ◽

Treatment Principle ◽

Severe Type ◽

Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a common and most severe type of Motor Neuron Disease. It is characterized by progressive skeletal muscle weakness, wasting and fasciculations. Survival is for 3-5 years, and the death is from respiratory paralysis. The incidence of ALS is between 0.6 and 3.8 per 100000 persons per year. Males are predominantly affected. Here is a case report of 45yrs old male who presented with complaints of difficulty in walking since 3years, with an insidious asymmetric onset of weakness of bilateral lower limbs with wasting and fasciculations. In Ayurveda, the case was symptomatologically diagnosed as Mamsa Sosha, which occurs as the result of obstruction of Snayu and Rakthadhamanis (Mamsavaha srotomoolas). The assessment was done using ALSFRS-R Scale. The treatment was aimed at improving the quality of life and also decreasing the rate of disease progression. The treatment principle adopted was Srothosodhana (Ama- Avaranaghna cikitsa) and Brimhana. Promising results were obtained after treatment. Keywords: ALS, MND, Ayurveda, Avaranaghna cikitsa, Mamsa Sosha, Mamsa Kshaya

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