RRC ID 68415
Author Yamagishi S, Koyama Y, Katayama T, Taniguchi M, Hitomi J, Kato M, Aoki M, Itoyama Y, Kato S, Tohyama M.
Title An in vitro model for Lewy body-like hyaline inclusion/astrocytic hyaline inclusion: induction by ER stress with an ALS-linked SOD1 mutation.
Journal PLoS One
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.
Volume 2(10)
Pages e1030
Published 2007-10-10
DOI 10.1371/journal.pone.0001030
PMID 17925878
Human and Animal Cells SK-N-SH(RCB0426)