論文 - 詳細
| RRC ID | 68415 |
|---|---|
| 著者 | Yamagishi S, Koyama Y, Katayama T, Taniguchi M, Hitomi J, Kato M, Aoki M, Itoyama Y, Kato S, Tohyama M. |
| タイトル | An in vitro model for Lewy body-like hyaline inclusion/astrocytic hyaline inclusion: induction by ER stress with an ALS-linked SOD1 mutation. |
| ジャーナル | 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. |
| 巻・号 | 2(10) |
| ページ | e1030 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | SK-N-SH(RCB0426) |