A nasal injection of adiponectin: a novel therapeutic strategy against neurodegenerative disease
Project/Area Number |
25640030
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
HASHIMOTO Makoto 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野., 副参事研究員 (50189502)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | αシヌクレイン / βシヌクレイン / パーキンソン病 / アルツハイマー病 / アディポネクチン / レビー小体型認知症 / 神経変性疾患 / 鼻腔投与 / アディポネクチン(APN) / αシヌクレイン(αS) / パーキンソン病(PD) / トランスジェニック(tg)マウス / シヌクレイン / 糖尿病 |
Outline of Final Research Achievements |
Neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. To investigate possible roles of adiponectin (APN), the anti-diabetes protein, in the pathogenesis of α-synucleinopathies, we investigated autopsy brain of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse models of α-synucleinopathies.In autopsy brains, APN was localized in Lewy bodies derived from PD and DLB. In neuronal cells expressing α-synuclein (αS), aggregation of αS was suppressed by treatment with recombinant APN in an AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and release of αS were significantly decreased by APN. In αS transgenic mice, both histopathology and movement disorder were significantly improved by intra nasal treatment with globular APN. Collectively, APN could possess a therapeutic potential against α-synucleinopathies.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Disease-Modifying Effect of Adiponectin in Model of α-Synucleinopathie2014
Author(s)
Sekiyama K, Waragai M, Akatsu H, Sugama S, Takenouchi T, Takamatsu Y, Fujita M, Sekigawa A, Rockenstein E, Inoue S, La Spada A, Masliah E, Hashimoto M
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Journal Title
Ann Clin Transl Neurol
Volume: 1
Issue: 7
Pages: 479-489
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Disease Modifying Effect of Adiponectin in a Model of α-Synucleinopathies in Vitro and in Vivo.2015
Author(s)
Masaaki Waragai, Kazunari Sekiyama, Yoshiki Takamatsu, Masayo Fujita, Akio Sekigawa, Naomichi Iwai, Edward Rockenstein, Satoshi Inoue, Albert R. La Spada, Elizer Masliah, Makoto Hashimoto
Organizer
Alzheimer's Association International Conference (AAIC2015)
Place of Presentation
Washington D.C., USA
Year and Date
2015-07-18
Related Report
Int'l Joint Research
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