期刊
NEUROCHEMISTRY INTERNATIONAL
卷 56, 期 2, 页码 216-220出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2009.12.005
关键词
Homocysteine; X-box-binding protein 1; Neurodegenerative disease; Endoplasmic reticulum stress; GRP78; CHOP
资金
- Ministry of Education, Science, Sports and Culture, Japan
- Institute of Laboratory Animal Science (Hiroshima University)
Increasing evidence has been suggested that hyperhomocysteinemia is a risk factor of neurodegenerative diseases, although, the underlying mechanisms have not been elucidated. Here, we found peripheral application of homocysteine increases X-box-binding protein 1 (XBP1) splicing in the several areas of the mice brain, such as hippocampus, hypothalamus and cortex. Time-course experiments indicated that XBP1 splicing was observed from 2 h, which was decreased thereafter. On the other hand, we did not observe GRP78 or CHOP induction in homocysteine-treated mice brain. As XBP1 is spliced in response to endoplasmic reticulum (ER) stress and ER stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease and Parkinson's disease, homocysteine-induced XBP1 splicing would be a key mechanism for such diseases. (C) 2009 Elsevier Ltd. All rights reserved.
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