14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis

Brain Res. 2016 Sep 1:1646:132-138. doi: 10.1016/j.brainres.2016.05.051. Epub 2016 May 30.

Abstract

The immunolocalization of the 14-3-3 eta isoform in the anterior horn cells (AHCs) of patients with sporadic amyotrophic lateral sclerosis (ALS) and controls was examined. Compared with the immunolocalization of other 14-3-3 isoforms, the immunolocalization of the 14-3-3 eta isoform was either synaptic at the periphery of AHCs, spindle-shaped in neurites, or granular in the cytoplasm. By double labeling with phosphorylated (p-)TDP-43, the transactivation response DNA binding protein of 43kDa (TDP-43) demonstrated frequent colocalization of the 14-3-3 eta isoform in granular structures (90%) and spindle-shaped structures (85.4%), but not in p-TDP-43-positive round inclusions. It is speculated that the 14-3-3 eta isoform is associated with not only a synaptic pathology of ALS but also TDP-positive small lesions in the cytoplasm and neurites. The absence of eta-like immunoreactivity in p-TDP-43-positive large inclusions suggests the restricted relevance of the 14-3-3 eta isoform during ALS pathogenesis to some phases of the p-TDP pathology.

Keywords: 14-3-3 proteins; Amyotrophic lateral sclerosis; Anterior horn cells; Eta isoform; SNAP25; TDP-43.

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Aged
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Anterior Horn Cells / metabolism*
  • Cytoplasmic Granules / metabolism
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurites / metabolism
  • Protein Isoforms / metabolism

Substances

  • 14-3-3 Proteins
  • DNA-Binding Proteins
  • Protein Isoforms
  • TARDBP protein, human
  • YWHAH protein, human