2013 Fiscal Year Final Research Report
Analysis of underlying mechanism to develop Alzheimer's disease
| Project/Area Number |
23617007
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Integrated Nutrition Science
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 小胞体ストレス / ATF4 / GADD34 / eIF2alpha / アミロイドーベータ |
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| Research Abstract |
Gamma-secretase produces amyloid-beta (Ab) in the brain from Ab precursor protein, which is critical for tha pathogenesis of Alzheimer's disease (AD). The endoplasmic reticulum (ER) stress causes unfolded proteins, which are processed by unfolded protein response (UPR). Pathogenesis of obesity and diabetes, which are risk factors for AD, is related to ER stress. However, whether ER stress is engaged in the development of AD remains obscure. In this research, I showed that ER stress activated gamma-secretase, leading to augmentation of Ab through induction of activating transcription factor 4 (ATF4). Ab secretion was repressed in vitro by quercetin, which induced the growth arrest and DNA damaged-inducible gene (GADD)34. In addition, we found that phosphorylated eIF2alpha and ATF4 were increased in the brain of AD model mice APP23. These results suggest that ER stress signaling may be disturbed in the brain of AD.
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Research Products
(12 results)
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[Journal Article] Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax2014
Author(s)
M asashi Ueda, Shimo Li, Masanori Itoh, Yoshika Hayakawa-Yano, Miao-xing Wang, Miki Hayakawa, Ryoko Hasebe-Matsubara, Kazunori Ohta, Eri Ohta, Akihito Mizuno, Yoko Hida, Munekazu Matsumoto, Huayue Chen, Toshiyuki Nakagawa
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Journal Title
Biochem Biophys Res Commun
Volume: 443
Pages: 1232-1238
Peer Reviewed
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[Journal Article] Endoplasmic reticulum stress enhancesγ-secretase activity2011
Author(s)
Ohta K, Mizuno A, Li S, Itoh M, Ueda M, Ohta E, Hida Y, Wang MX, Furoi M, Tsuzuki Y, Sobajima M, Bohmoto Y, Fukushima T, Kobori M, Inuzuka T, Nakagawa T
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Journal Title
Biochem Biophys Res Commun
Volume: 416
Pages: 362-366
Peer Reviewed
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[Presentation] Endoplasmic reticulum stress leads to increase gamma-secretase activity and beta-amyloid production2011
Author(s)
Kazunori Ohta, Akihito Mizuno, Shimo Li, Masashi Ueda, Masanori Itoh, Eri Ohta, Yoko Hida, Miao-xing Wang , Manabu Furoi, Yukihiro Tuzuki, Mituaki Sobajima, Yoshimasa Bohmoto, Tatsuya Fukushima, Toshituki Nakagawa
Organizer
第34回日本分子生物学会年会
Place of Presentation
横浜(3P-701)
Year and Date
2011-12-15
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[Presentation] A novel regulation mechanism of synaptic transmission by preseynapse-localizing Caymanataxia-related protein,Caytaxin2011
Author(s)
Masanori itoh, Shimo Li, Kazunori Ohta, Masashi Ueda, Yoko Hida, Yoshihiro Suzuki, Eri Ohta, Akihito Mizuno, Miao-xing Wang, Toshiyuki Nakagawa
Organizer
第34回日本分子生物学会年会
Place of Presentation
横浜(1P-0921)
Year and Date
2011-12-13
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[Presentation] The expression and localization of Prune2 and its novel isoform in the central neuvous system2011
Author(s)
S.LI, M.ITOH, K.OHTA, M.UEDA, A.MIZUNO, E.OHTA, Y.HIDA, M.WANG, K.YAKEUCHI, T.NAKAGAWA
Organizer
41th ANNUAL MEETING Neuroscience2011
Place of Presentation
Washington DC, USA
Year and Date
2011-11-12
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