Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

Biochim Biophys Acta. 2014 Jan;1842(1):99-106. doi: 10.1016/j.bbadis.2013.10.013. Epub 2013 Oct 30.


Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS.

Keywords: 2DE; ALS; Amyotrophic lateral sclerosis; CNS; LC-ESI-MS/MS; M; MN; MyBP-H; Myosin binding protein H; Skeletal muscle; WB; Western blot; amyotrophic lateral sclerosis; central nervous system; liquid chromatography electron spray ionization tandem mass spectrometry; motor neuropathies; myopathies; two-dimensional electrophoresis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnosis
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cofilin 2 / genetics
  • Cofilin 2 / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Lim Kinases / genetics
  • Lim Kinases / metabolism
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • Myosins / genetics*
  • Myosins / metabolism
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / pathology
  • Protein Binding
  • Proteomics
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism


  • Biomarkers
  • CFL2 protein, human
  • Cofilin 2
  • Cytoskeletal Proteins
  • MYBPH protein, human
  • LIMK1 protein, human
  • Lim Kinases
  • ROCK2 protein, human
  • rho-Associated Kinases
  • Myosins

Supplementary concepts

  • Amyotrophic lateral sclerosis 1
  • Inherited Peripheral Neuropathy