An in vitro model for lewy body-like hyaline inclusion/astrocytic hyaline inclusion: Induction by ER stress with an ALS-linked SOD1 mutation

Satoru Yamagishi, Yoshihisa Koyama, Talichi Katayama, Manabu Taniguchi, Junichi Hitomi, Masaaki Kato, Masashi Aoki, Yasuto Itoyama, Shinsuke Kato, Masaya Tohyama

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27 Citations (Scopus)

Abstract

Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast-HI) containing mutant Cu/Zn superoxide dismutase 1 (SOD1) are morphological hallmarks of familial amyotrophic lateral sclerosis (FALS) associated with mutant SOD1. However, the mechanisms by which mutant SOD1 contributes to formation of LBHI/Ast-HI in FALS remain poorly defined. Here, we report induction of LBHI/Ast-HI-like hyaline inclusions (LHIs)-in vitro by ER stress in neuroblastoma cells. These LHI closely resemble LBHI/Ast-HI in patients with SOD1-linked FALS. LHI and LBHI/Ast-HI share the following features: 1) eosinophilic staining with a pale core, 2) SOD1, ubiquitin and ER resident protein (KDEL) positivity and 3) the presence of approximately 15-25 nm granule-coated fibrils, which are morphological hallmark of mutant SOD1-linked FALS. Moreover, in spinal cord neurons of L84V SOD1 transgenic mice at presymptomatic stage, we observed aberrant aggregation of ER and numerous free ribosomes associated with abnormal inclusion-like structures, presumably early stage neuronal LBHI. We conclude that the LBHI/Ast-HI seen in human patients with mutant SOD1-linked FALS may arise from ER dysfunction.

Original languageEnglish
Article numbere1030
JournalPloS one
Volume2
Issue number10
DOIs
Publication statusPublished - 2007 Oct 10

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yamagishi, S., Koyama, Y., Katayama, T., Taniguchi, M., Hitomi, J., Kato, M., Aoki, M., Itoyama, Y., Kato, S., & Tohyama, M. (2007). An in vitro model for lewy body-like hyaline inclusion/astrocytic hyaline inclusion: Induction by ER stress with an ALS-linked SOD1 mutation. PloS one, 2(10), [e1030]. https://doi.org/10.1371/journal.pone.0001030