2002 Fiscal Year Final Research Report Summary
Biochemical characterization of tau in tauopaty brains
| Project/Area Number |
12680727
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 Organization for Medical Research (2001-2002)
The University of Tokyo (2000) |
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Principal Investigator |
HASEGAWA Masato TOKYO INSTITUTE OF PSYCHIATRY,HEAD, 東京都精神医学総合研究所, 副参事研究員 (10251232)
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| Co-Investigator(Kenkyū-buntansha) |
IWATSUBO Takeshi UNIVERSITY OF TOKYO, PROFESSOR, 大学院・薬学系研究科, 教授 (50223409)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Tau / Phosphorylation / splicing / α-synuclein / Neurodegenrative disease / Cdk5 |
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| Research Abstract |
(1)Biochemical characterization of tau from tauopathy brains
We investigated effects of tau gene mutations (Exon10+11, +12, N279K, R5H, L266V) which were identified in Japanese families by analyzing soluble and insoluble tau from the patients, exon trapping assay and in vitro microtubule assembly assay. Hyperphosphorylated 4-repeat (4R) tau depositions were observed in brains of patients with either Exon10+12 or N279. Both R5H and L266V mutations affected the ability to promote microtubule assembly, and tau deposition of both 3R and 4R isoforms were detected in those brains. Analysis of soluble and insoluble tau from patients with Kii ALS-PDC revealed hyperphosphorylated 3R and 4R tau accumulations and normal pattern of soluble tau.
(2)Cdk5 activator p25 in AD brains
We investigated whether Cdk5 activator p25 that is produced by calpain cleavage of p35 is elevated in AD brain. Analysis of 8 AD and 9 control cases have shown that no significant increase of p25 was detected in AD brain. Furthermore, we clearly showed that p35 degraded to p25 during postmortem intervals.
(3)Posttranslational modification on α-synuclein
We analyzed α-synuclein deposited in brains with dementia with Lewy body patients using biochemical and proteinchemical techniques, and identified that the insoluble α-synuclein is hyperphosphorylated at Ser129. We also found that a fraction of phosphorylated insoluble α-synuclein is ubiquitinated in α-synucleinopathy lesions, and that amino acid residues 31-109 of α-synuclein constitute Proteinase K resistant core of the filaments
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Research Products
(23 results)
