A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies)

• Takano, Katsura

• Kitao, Yasuko

• Inagi, Reiko

• Momoi, Takashi

• Matsuyama, Tomohiro

• Miyata, Toshi

• Yoneda, Yukio

• Iso, Hiroyuki

• Stern, David M.

• Hori, Osamu

• Ogawa, Satoshi

抄録

金沢大学大学院医学系研究科脳細胞分子学

FENIB (familial encephalopathy with neuroserpin inclusion bodies) is caused by intracellular accumulation/polymerization of mutant neuroserpins in the endoplasmic reticulum (ER). Transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS)-positive inclusions distributed throughout deeper layers of cerebral cortex, CA1 of the hippocampus, and substantia nigra. Hippocampal extracts from Tg meg rats showed increased expression of ER stress proteins, and activation of caspases-12 and -3, associated with decreased neuronal density. Enhanced ER stress was also observed in dopaminergic neurons in the substantia nigra, in parallel with decreased neuronal viability and motor coordination. In each case, PAS-positive inclusions were also positive for megsin. These data suggest that overexpression of megsin results in ER stress, eventuating in the formation of PAS-positive inclusions. Tg meg rats provide a novel model of FENIB, where accumulation of serpins in the ER induces selective dysfunction/loss of specific neuronal populations. © 2006 Elsevier Inc. All rights reserved.

収録刊行物

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 346 (3), 1040-1047, 2006-04-01

  Elsevier

キーワード

• Neuronal cell death
• Neuroserpin
• Oxidant stress
• Oxygen/glucose regulated protein (ORP/GRP）
• Protein malfolding

詳細情報

• CRID: 1050282810924792064
• NII論文ID: 120000809734
• ISSN: 0006291X
• Web Site: http://hdl.handle.net/2297/2867
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • CiNii Articles