1993 Fiscal Year Final Research Report Summary
Molecular Biology of Nervous Disorders caused by Amyloid
| Project/Area Number |
04404027
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAKAKI Yoshiyuki The Univ. of Tokyo, The Inst. of Medical Science, Professor, 医科学研究所, 教授 (10112327)
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| Co-Investigator(Kenkyū-buntansha) |
TEI Hajime The Univ. of Tokyo, The Inst. of Medical Science, Joshu, 医科学研究所, 助手 (00242115)
HATTORI Masahira The Univ. of Tokyo, The Inst. of Medical Science, Associate Professor, 医科学研究所, 助教授 (70175537)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Amyloidosis / Alzheimer's disease / Transthyretin / Beta amyloid / Transgenic mice / X-ray crystallography / Genetic disease |
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| Research Abstract |
We have studied on familial amyloidotic polyneuropathy(FAP)and Alzheimer's disease(AD)
FAP : we produced large amount of recombinant Met-30 type transthyretin which causes type IFAP, and crystallized it. The TTR crystal was analyzed by X-ray diffraction in collaboration with Drs Collin Blake and Maria Joao Saraiva. The results showed that Cys-recidue at the position 10 was free in the Met-30 TTR, While it interacted with the amino acid recidue at 57 in the wild type TTR.We suggested that the intermolecular S-S bridge formation may trigger the amyloid formation. Transgenic mice study on this hypothesis is in progress.
AD : We constructed transgenic mice carrying NFS promoter-App 717 varrant fusion gene and NSF promoter-APP C-100 fusion gene.Those mice showed high expression of the transgenes at mRNA level but no pathological abnormality was observed at the stage of 12 months old.
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Research Products
(12 results)
