The study of modulation of neuronal cell death and searching for new functional molecule regulated by endoplasmic reticulum stress and by innate immune system
| Project/Area Number |
16590040
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | CHIBA INSTITUTE OF SCIENCE (2005)
Hokkaido University (2004) |
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Principal Investigator |
OKUMA Yasunobu Chiba Institute of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20127939)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMA Yasunobu Chiba Institute of Science, Faculty of Pharmaceutical Sciences, Professor (20127939)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | neuronal cell death / ER stress / innage immunity / chemical chaperon / 4-phenylbutylate / 脳虚血 / フェニル酪酸 |
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| Research Abstract |
Recent studies have shown that neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are involved in a disruption of endoplasmic reticulum (ER) function. We investigated the effects of 4-phenylbutylate (4-PBA) on the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R) pathologically relevant to the loss of dopaminergic neurons in autosomal recessive juvenile Parkinsonism (AR-JP). 4-PBA restored the normal expression of Paer-R protein and suppressed ER stress induced by the accumulation of Paer-R. In addition, we showed that 4-PBA attenuated the activation of ER-stress-induced signal transduction pathways and subsequent neuronal cell death. Furthermore, we revealed that 4-PBA possesses chemical chaperon activity in vitro, which prevents the aggregation of denatured α-lactalbumin and bovine serum albumin (BSA).
Epidemiological evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Parkinson's disease and Alzheimer's disease. However, the mechanism (s) by which NSAIDs elicit their anti-neurodegenerative effects is not clear. We found that pretreatment with aspirin significantly inhibited tunicamycin-induced ER-stress response such as XBP-1 mRNA splicing and induction of GRP78 and CHOP. Furthermore, we demonstrated that aspinin directly inhibited the aggregation of reduced α-lactalbumin and BSA, indicating the possibility that aspirin act as a chemical chaperone.
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Report
(3 results)
Research Products
(30 results)
