Molecular mechanism of alpha-synuclein aggregation in Lewy body disease
Project/Area Number |
24300131
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Hirosaki University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
TANJI Kunikazu 弘前大学, 大学院医学研究科, 助教 (10271800)
MIKI Yasuo 弘前大学, 大学院医学研究科, 助教 (30709142)
MORI Fumiaki 弘前大学, 大学院医学研究科, 准教授 (60200383)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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Keywords | パーキンソン病 / レビー小体 / オートファジー / 神経変性疾患 / 脳神経疾患 / 神経科学 / 病理学 |
Outline of Final Research Achievements |
In Lewy body disease (LBD), insoluble alpha-synuclein (AS) is widely deposited in the presynaptic terminals as well as in the neuronal cytoplasm. To test the possibility that activated autophagy can degrade abnormal molecules, we investigated the effect of trehalose on abnormal aggregation of AS in a model of LBD. Trehalose is a natural disaccharide composed of two glucose units. Trehalose increased level of the autophagosomal protein LC3, especially a lipidated form LC3-II in cultured cells and mice brain. Also, trehalose increased levels of several chaperon molecules, such as HSP90 and SigmaR1, in the brains of LBD model mice. Further studies revealed that level of detergent insoluble AS was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of AS. These results suggest that oral intake of trehalose modulates propensity of molecules prior to aggregation formation.
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Report
(5 results)
Research Products
(49 results)
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[Journal Article] Accumulation of phosphorylated alpha-synuclein in subpial and periventricular astrocytes in multiple system atrophy of long duration2016
Author(s)
Nakamura K, Mori F, Kon T, Tanji K, Miki Y, Tomiyama M, Kurotaki H, Toyoshima Y, Kakita A, Takahashi H, Yamada M, Wakabayashi K.
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Journal Title
Neuropathology
Volume: -
Issue: 2
Pages: 157-167
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease2016
Author(s)
Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
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Journal Title
Brain Pathol
Volume: -
Issue: 3
Pages: 359-370
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] p62 Deficiency Enhances α-Synuclein Pathology in Mice.2015
Author(s)
Tanji K, Odagiri S, Miki Y, Maruyama A, Nikaido Y, Mimura J, Mori F, Warabi E, Yanagawa T, Ueno S, Itoh K, Wakabayashi K.
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Journal Title
Brain Pathol.
Volume: 印刷中
Issue: 5
Pages: 552-564
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is localized in Lewy bodies2015
Author(s)
Nakamura K, Mori F, Tanji K, Miki Y, Yamada M, Kakita A, Takahashi H, Utsumi J, Sasaki H, Wakabayashi K
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Journal Title
Neuropathol
Volume: 35
Issue: 5
Pages: 432-440
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Localization of nuclear receptor subfamily 4, group A, member 3 (NR4A3) in Lewy body disease and multiple system atrophy2015
Author(s)
Kon T, Miki Y, Tanji K, Mori F, Tomiyama M, Toyoshima Y, Kakita A, Takahashi H, Utsumi J, Sasaki H, Wakabayashi K
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Journal Title
Neuropathology
Volume: 35
Issue: 6
Pages: 503-509
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Filamentous aggregations of phosphorylated α-synuclein in Schwann cells (Schwann cell cytoplasmic inclusions) in multiple system atrophy2015
Author(s)
Nakamura K, Mori F, Kon T, Tanji K, Miki Y, Tomiyama M, Kurotaki H, Toyoshima Y, Kakita A, Takahashi H, Yamada M, Wakabayashi K
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Journal Title
Acta Neuropathol Commun
Volume: 3
Issue: 1
Pages: 29-29
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Phosphorylation of serine 349 of p62 in Alzheimer’s disease brain2014
Author(s)
Tanji K, Miki Y, Ozaki T, Maruyama A, Yoshida H, Mimura J, Matsumiya T, Mori F, Imaizumi T, Itoh K, Kakita A, Takahashi H, Wakabayashi K
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Journal Title
Acta Neuropathol Comm
Volume: 2
Issue: 1
Pages: 50-50
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] ALS-associated protein FIG4 is localized in Pick and Lewy bodies, and neuronal nuclear inclusions in polyglutamine and intranuclear inclusion body diseases.2014
Author(s)
Kon T, Mori F, Yanji F, Miki Y, Toyoshima Y, Yoshida M, Sasaki H, Kakita A, Takahashi H, Wakabayashi K
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Journal Title
Neuropathology
Volume: 34
Issue: 1
Pages: 19-26
DOI
Related Report
Peer Reviewed
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[Journal Article] Lysosomal storage and advanced senescence in the brain of LAMP-2-deficient Danon disease2013
Author(s)
Furuta A, Wakabayashi K, Haratake J, Kikuchi H, Kabuta T, Mori F, Tokonami F, Katsumi Y, Tanioka F, Uchiyama Y, Nishino I, Wada K
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Journal Title
Acta Neuropathol
Volume: 125
Issue: 3
Pages: 459-461
DOI
Related Report
Peer Reviewed
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[Journal Article] Ubiquilin immunoreactivity in cytoplasmic and nuclear inclusions in synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease.2012
Author(s)
Mori F, Tanji K, Odagiri S, Toyoshima Y, Yoshida M, Ikeda T, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
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Journal Title
Acta Neuropathol
Volume: 124
Issue: 1
Pages: 149-151
DOI
Related Report
Peer Reviewed
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[Presentation] MSAとオートファジー2014
Author(s)
若林孝一
Organizer
第55回日本神経学会
Place of Presentation
福岡国際会議場(福岡市)
Year and Date
2014-05-21 – 2014-05-24
Related Report
Invited
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