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
|
PMC |
PMC2000355
|
MeSH |
Amyotrophic Lateral Sclerosis / genetics*
Animals
Astrocytes / cytology*
Cell Line, Tumor
Endoplasmic Reticulum / metabolism*
Golgi Apparatus / metabolism
Humans
In Vitro Techniques
Lewy Bodies / metabolism*
Lysosomes / metabolism
Mice
Mice, Transgenic
Mutation*
Ribosomes / metabolism
Superoxide Dismutase / genetics*
Superoxide Dismutase-1
Ubiquitin / chemistry
|
IF |
2.74
|
Resource |
Human and Animal Cells |
SK-N-SH(RCB0426) |