Distinct biochemical signatures characterize peripherin isoform expression in both traumatic neuronal injury and motor neuron disease

J Neurochem. 2010 Aug;114(4):1177-92. doi: 10.1111/j.1471-4159.2010.06846.x. Epub 2010 Jun 1.


Peripherin is a type III intermediate filament protein that is up-regulated during neuronal injury and is a major component of pathological inclusions found within degenerating motor neurons of patients with amyotrophic lateral sclerosis (ALS). The relationship between these inclusions and their protein constituents remains largely unknown. We have previously shown that peripherin expression is characterized by tissue-specific, intra-isoform associations that contribute to filament structure; changes to the normal isoform expression pattern is associated with malformed filaments and intracellular inclusions. Here, we profile peripherin isoform expression and ratio changes in traumatic neuronal injury, transgenic mouse models of motor neuron disease, and ALS. Extensive western blot analyses of Triton X-100 soluble and insoluble fractions of neuronal tissue from these conditions revealed significant changes in peripherin isoform content which could be differentiated by electrophoretic banding patterns to produce distinct peripherin biochemical signatures. Significantly, we found that the pattern of peripherin expression in ALS most closely approximates that of peripherin over-expressing mice, but differs with regard to inter-individual variations in isoform-specific expression. Overall, these results provide important insights into complex post-transcriptional processes that may underlie a continuum between peripherin-mediated neuronal repair and its role in the pathogenesis of motor neuron disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Biomarkers / metabolism
  • Brain Injuries / etiology
  • Brain Injuries / physiopathology
  • Disease Models, Animal*
  • Gene Expression Regulation / physiology
  • Intermediate Filament Proteins / biosynthesis
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / metabolism*
  • Motor Neuron Disease / physiopathology
  • Nerve Crush / methods
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Peripherins
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Proteomics
  • Sciatic Nerve / pathology


  • Biomarkers
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Peripherins
  • Protein Isoforms