Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions

Hiroyuki Honda, Hideomi Hamasaki, Tomihiro Wakamiya, Sachiko Koyama, Satoshi O. Suzuki, Naoki Fujii, Toru Iwaki

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons and appearance of skein-like inclusions. The inclusions are composed of trans-activation response (TAR) DNA-binding protein 43 (TDP-43), a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPA1 and hnRNPA2/B1 are hnRNPs that interact with the C-terminus of TDP-43. Using immunohistochemistry, we investigated the association between TDP-43 and hnRNPA1 in ALS spinal motor neurons. We examined spinal cords of seven ALS cases and six muscular dystrophy cases (used as controls) for the presence of TDP-43 and hnRNPA1 protein. In the control cases, hnRNPA1 immunoreactivity in motor neurons was intense in the nucleus and weak in the cytoplasm where it showed a fine granular appearance. In the ALS cases, hnRNPA1 immunoreactivity in motor neurons was reduced in the nuclei of neurons with skein-like inclusions but was not detected in the skein-like inclusions. The marked loss of hnRNPA1 in motor neurons with concomitant cytoplasmic aggregation of TDP-43 may represent a severe disturbance of mRNA processing, suggesting a key role in progressive neuronal death in ALS.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalNeuropathology
Volume35
Issue number1
DOIs
Publication statusPublished - Feb 1 2015

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology

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