| Project/Area Number |
25290019
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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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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| Co-Investigator(Kenkyū-buntansha) |
小柳 清光 信州大学, 医学部, 教授 (00134958)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | アディポネクチン / 神経変性疾患 / パーキンソン病 / αシヌクレイン / アルツハイマー病 / アディポネクチン (APN) / パーキンソン病 (PD) / シヌクレイノパチー / αシヌクレイン (αS) / β-シヌクレイン(βS) / APPL1 / シヌクレイン / 糖尿病 |
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| Outline of Final Research Achievements |
Growing evidence suggests that neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. We investigated autopsy brain of α-synucleinopathies including Parkinson's disease and dementia with Lewy bodies, and analyzed the effects of adiponectin (APN) in cellular and in mouse models of α-synucleinopathies.
We observed that APN is localized in Lewy bodies derived from the brains of α-synucleinopathies. 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 transgenic mice expressing αS, both histopathology and movement disorder were improved by intranasal treatment with globular APN.
Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway in α-synucleinopathies.
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