Amyotrophic lateral sclerosis (ALS) is progressive neurological disease that results in the death of motor neurons in the brain and spinal cord, leading to a decrease in skeletal muscle size and muscle weakness, wasting, or paralysis. Most research on ALS has focused on motor neuron death, and the underlying mechanisms are not well understood. This study examined the molecular mechanisms underlying muscle degeneration. We compared the protein and cytokine profiles of gastrocnemius muscle in ALS model hSOD1G93A mice at pre-symptomatic and symptomatic stages by western blotting. Pro-inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and cluster of differentiation 11b were upregulated in the muscle of symptomatic as compared to pre-symptomatic mice. Additionally, the levels of oxidative stress-related proteins, heme oxygenase-1 and ferritin, were increased in muscle from symptomatic as compared to pre-symptomatic mice. We also observed increased autophagy dysfunction and metabolic dysregulation in the muscles of symptomatic hSOD1G93A as compared to non-Tg and pre-symptomatic hSOD1G93A mice, which was accompanied by upregulation of thrombospondin- 1, Prospero-related homeobox 1, glial fibrillary acidic protein, and DNA-damage-inducible 45α. Increased inflammation, oxidative stress, and autophagy contribute to motor neuron death and muscle atrophy in ALS, and the factors involved in these processes are potential therapeutic targets for treatment of this disease.

Introduction
Materials and Methods
    Animals
    Western blotting
    Statistical analysis
Results
    Upregulation of inflammatory proteins in the gastrocnemiusmuscle of symptomatic hSOD1G93A mice
    Changes of oxidative stress-related proteins in thegastrocnemius muscle of symptomatic hSOD1G93AmiceOxidative
    Autophagy dysfunction in the gastrocnemius muscleof symptomatic hSOD1G93A mice
    Alterations in gastrocnemius muscle metabolism insymptomatic hSOD1G93A mice
    Upregulation of atrophy-related proteins in thegastrocnemius muscle of symptomatic hSOD1G93Amice
Discussion
References

• Mudan Cai(Department of Herbal Medicine Research, Korea Institute of Oriental Medicine)
• Eun Jin Yang(Department of Clinical Research, Korea Institute of Oriental Medicine) Corresponding author