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Archives of Biochemistry and Biophysics


Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by motor neuron loss and prominent skeletal muscle wasting. Despite more than one hundred years of research efforts, the pathogenic mechanisms underlying neuromuscular degeneration in ALS remain elusive. While the death of motor neuron is a defining hallmark of ALS, accumulated evidences suggested that in addition to being a victim of motor neuron axonal withdrawal, the intrinsic skeletal muscle degeneration may also actively contribute to ALS disease pathogenesis and progression. Examination of spinal cord and muscle autopsy/biopsy samples of ALS patients revealed similar mitochondrial abnormalities in morphology, quantity and disposition, which are accompanied by defective mitochondrial respiratory chain complex and elevated oxidative stress. Detailing the molecular/cellular mechanisms and the role of mitochondrial dysfunction in ALS relies on ALS animal model studies. This review article discusses the dysregulated mitochondrial Ca2+ and reactive oxygen species (ROS) signaling revealed in live skeletal muscle derived from ALS mouse models, and a potential role of the vicious cycle formed between the dysregulated mitochondrial Ca2+ signaling and excessive ROS production in promoting muscle wasting during ALS progression.



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ALS, Autophagy, Mitochondria ROS, Mitochondrial Ca(2+) uptake, Mitochondrial dynamics, Skeletal muscle