2011年10月
Protein disulfide isomerase immunopositive glial cytoplasmic inclusions in patients with multiple system atrophy.
The International journal of neuroscience
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- 巻
- 121
- 号
- 10
- 開始ページ
- 543
- 終了ページ
- 50
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.3109/00207454.2011.585440
- 出版者・発行元
- INFORMA HEALTHCARE
BACKGROUND: Glial cytoplasmic inclusions (GCIs) are the pathological hallmarks of multiple system atrophy (MSA) and α-synuclein is abnormally deposited in GCIs. Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily and is believed to accelerate the folding of disulfide-bonded proteins by catalyzing the disulfide interchange reaction, which is the rate-limiting step during protein folding in the luminal space of the endoplasmic reticulum (ER). Nitric-oxide-induced (NO-induced) S-nitrosylation of PDI inhibits its enzymatic activity, leading to the accumulation of polyubiquitinated proteins, and activates the unfolded protein response in neurodegenerative diseases. MATERIALS AND METHODS: Postmortem brain specimens from five patients with MSA and five normal control brains were utilized in this immunohistochemical study. RESULTS: We found GCIs positive for anti-PDI antibody in the brain of patients with MSA. In addition, we observed colocalization of α-synuclein and leucine-rich repeat kinase 2 (LRRK2) with PDI in GCIs. As LRRK2 immunoreactivity is associated with one of the earliest oligodendrocytic abnormalities in MSA, colocalization of LRRK2 and PDI in GCIs may be a link to the ER stress of glial cells in the early stages of MSA. CONCLUSIONS: In MSA, NO may inhibit PDI by inducing S-nitrosylation, which inhibits its enzymatic activity and thus allows protein misfolding to occur.
- リンク情報
- ID情報
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- DOI : 10.3109/00207454.2011.585440
- ISSN : 0020-7454
- PubMed ID : 21689057
- Web of Science ID : WOS:000295219100002