2013 Fiscal Year Final Research Report
Development of novel therapeutic strategies against neurodegenerative diseases targeting on abnormal protein aggregates
| Project/Area Number |
23700433
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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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 |
MASUDA-SUZUKAKE Masami (増田 雅美) 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, 研究員 (20583751)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 国際情報交流 / αシヌクレイン / 神経変性疾患 / プリオン / パーキンソン病 / レビー小体型認知症 |
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| Research Abstract |
Alpha-Synuclein (asyn) is the major component of filamentous inclusions that constitute the defining characteristic of Parkinson's disease and dementia with Lewy bodies. However, the molecular mechanisms underlying asyn accumulation and spread are unclear.
In this study, we show that intracerebral injections of fibrils of recombinant asyn efficiently induced asyn pathologies in wild-type mice, whereas mice injected with soluble asyn did not. Immunoblot analysis demonstrated that endogenous mouse asyn started to accumulate 3 months after inoculation, while injected human asyn fibrils disappeared in about a week. These results indicate that asyn fibrils have prion-like properties and inoculation into wild-type brain induces asyn pathology in vivo. This is a new mouse model of sporadic asynucleinopathy, and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy.
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[Journal Article] Dipeptide repeat proteins are present in the p62 positive inclusions in patients with Frontotemopral Lober Degeneration and Motor Neurone Disease associated with expansions in C9ORF722013
Author(s)
Mann DM, RollinsonS, Robinson A, Callister J, Snowden SJ, Gendron T, Petrucelli L, Masuda-Suzukake M, Hasegawa M, Davidson Y, Pickering-Brown S
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Journal Title
Acta Neuropathologica Communications
DOI
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 MA D, Saito Y, Hatsuta H, Murayama S, Hasegawa M
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Journal Title
Acta Neuropathologica Communications
Volume: 1
Pages: 54
DOI
Peer Reviewed
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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, MurayamaS, Mann DM, AkiyamaH, Hasegawa M
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Journal Title
Cell Rep.
Volume: 4(1)
Pages: 124-34
DOI
Peer Reviewed
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[Journal Article] Isomerase Pin1 Stimulates Dephosphorylation of Tau Protein at Cyclin-dependent Kinase (Cdk5)dependent Alzheimer Phosphorylation Sites2013
Author(s)
Kimura T, Tsutsumi K, Taoka M, Saito T, Masuda-Suzukake M, Ishiguro K, Plattner F, Uchida T, Isobe T, Hasegawa M, Hisanaga S
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Journal Title
J Biol Chem.
Volume: 288(11)
Pages: 7968-77
DOI
Peer Reviewed
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[Journal Article] Molecular analysis and biochemical classification of TDP-43 proteinopathy2012
Author(s)
Tsuji H, Arai T, Kametani F, Nonaka T, Yamashita M, Suzukake M, Hosokawa M, Yoshida M, Hatsuta H, Takao M, Saito Y, Murayama S, Akiyama H, Hasegawa M, Mann DM, Tamaoka A
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Journal Title
Brain.
Volume: 135
Pages: 3380-91
DOI
Peer Reviewed
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[Journal Article] Phosphorylated α-synuclein in Parkinson's disease2012
Author(s)
Wang Y, Shi M, Chung KA, Zabetian CP, Leverenz JB, Berg D, Srulijes K, Trojanowski JQ, Lee VM, Siderowf AD, Hurtig H, Litvan I, Schiess MC, Peskind ER, Masuda M, Hasegawa M, Lin X, Pan C, Galasko D, Goldstein DS, Jensen PH, Yang H, Cain KC, Zhang J
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Journal Title
Sci Transl Med.
Volume: 4(121)
Pages: 121ra20
DOI
Peer Reviewed
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