Dysregulation of Myosin Complex and Striated Muscle Contraction Pathway in the Brains of ALS-SOD1 Model Mice

Benhong Xu, Chengyou Zheng, Xiao Chen, Zaijun Zhang, Jianjun Liu, Peter Spencer, Xifei Yang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by cortical and spinal motor neuron degeneration, some inherited cases of which are caused by mutations in the gene coding for copper-zinc superoxide dismutase-1 (SOD1). The SOD1G93A mutant model mouse, which expresses large amounts of mutant SOD1, develops adult-onset neurodegeneration of spinal motor neurons and progressive motor deficits leading to paralysis. We used the Tandem Mass Tag technique to investigate the proteome profile of hippocampus, cerebral cortex, and medulla oblongata of the SOD1G93A mutant model mice as compared with that of wild-type (WT) mice. Fifteen proteins were significantly increased or decreased (i.e., changed) in all three tissues. Gene ontology analysis revealed that the changed proteins were mainly enriched in negative regulation of reactive oxygen species, myosin complex and copper ion binding. In the Striated Muscle Contraction Pathway, most of the identified proteins were decreased in the SOD1G93A mice compared with the WT mice. Myosin-1 (MYH1), fructose-2,6-bisphosphatase TIGAR (TIGAR), and sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (ATP2A1) were significantly reduced in mutant vs WT mice, as confirmed by Western blot analysis. Since myosins and tropomyosins are specific for synapse function and drive actin dynamics in the maturation of dendritic spines, changes in these proteins may contribute to perturbations of brain neuronal circuitry in addition to spinal motor neuron disease.

Original languageEnglish (US)
Pages (from-to)2408-2417
Number of pages10
JournalACS Chemical Neuroscience
Issue number5
StatePublished - May 15 2019


  • SOD1
  • amyotrophic lateral sclerosis
  • copper-zinc superoxide dismutase-1
  • muscle contraction
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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