2013 Fiscal Year Final Research Report
Molecular mechanisms of pathological protein propagation and its regulation
| Project/Area Number |
23240050
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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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 |
HASEGAWA Masato 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, 分野長 (10251232)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 神経変性疾患 / 伝播 / シヌクレイン / TDP-43 / タウ / プリオン |
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| Research Abstract |
Progressive neurodegeneration with accumulation of abnormal proteins is the defining neuropathological feature of many neurodegenerative diseases, including Lewy body disease (LBD) and ALS/FTLD. We revealed that injections of recombinant alpha-synuclein (aS) fibrils efficiently induced hyperphosphorylated aS pathology in wild-type mice. Biochemical analyses demonstrated that endogenous mouse aS started to accumulate 3 months after inoculation. Furthermore, injections of Sarkosyl-insoluble aS from LBD patients induced similar aS pathology, indicating that aS fibrils show prion-like infectivity. We also demonstrated that insoluble TDP-43 has prion-like properties. These results indicate that pathological proteins may play a role in the progression of neurodegenerative diseases with protein pathologies. These cellular and mouse models should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy.
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[Journal Article] Prion-like Properties of Pathological TDP-43 Aggregates from Diseased Brains2013
Author(s)
Nonaka T, Masuda-Suzukake M, Arai T, Hasegawa Y, Akatsu H, Obi T, Yoshida M, Murayama S, Mann DM, Akiyama H, Hasegawa
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Journal Title
Cell Rep
Volume: 4(1)
Pages: 124-34
Peer Reviewed
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[Journal Article] Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer's disease brain2013
Author(s)
Dan A, Takahashi M, Masuda-Suzukake M, Kametani F, Nonaka T, Kondo H, Akiyama H, Arai T, Mann DMA, Saito Y, Hatsuta H, Murayama S, Hasegawa M
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Journal Title
Acta Neuropathol. Commun
Volume: 1 (1)
Pages: 54
Peer Reviewed
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[Journal Article] Pin1 stimulates dephosphorylation of tau at Cdk5- dependent Alzheimer phosphorylation sites2013
Author(s)
Kimura T, Tsutsumi K, Taoka M, Saito T, Masuda-Suzukake M, Ishiguro K, Plattner F, Uchida T, Ishobe T, Hasegawa M, Hisanaga SI
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Journal Title
J. Biol. Chem
Volume: 288(11)
Pages: 7968 -77
Peer Reviewed
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[Journal Article] Molecular analysis and biochemical classification of TDP-43 proteinopathy2012
Author(s)
Tsuji1 H, Arai T, Kametani F, Nonaka T, Yamashita M, Suzukake M, Hosokawa M, Yoshida M, Hatsuta H, Takao M, Saito Y, Murayama M, Akiyama H, Hasegawa M, Mann DMA, Tamaoka A
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Journal Title
Brain
Volume: 135
Pages: 3380-3391
Peer Reviewed
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[Presentation] Insoluble TDP-43 prepared from diseased brains has prion-like properties2013
Author(s)
Nonaka T, Masuda-Suzukake M, Arai T, Hasegawa Y, Akatsu H, Obi T, Yoshida M, Murayama S, Mann DM, Akiyama H and Hasegawa M
Organizer
Alzheimer's Association International Conference (AAIC2013)
Place of Presentation
Boston, USA
Year and Date
2013-07-18
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