2005 Fiscal Year Final Research Report Summary
Degradation of amyloid-beta
| Project/Area Number |
16591132
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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 |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
TAGAMI Shinji Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Assistant, 医学系研究科, 助手 (40362735)
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| Co-Investigator(Kenkyū-buntansha) |
OKOCHI Masayasu Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Assistant, 医学系研究科, 助手 (90335357)
TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Department of Post-Genomics and Diseases, Professor, 医学系研究科, 教授 (00179649)
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| Project Period (FY) |
2004 – 2005
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| Keywords | BACE / Aβ degradation / γ-secretase / cell-free BACE assay |
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| Research Abstract |
Senile plaque is a pathological hallmark of Alzheimer's disease (AD) and its major component is amyloid-beta peptides (Aβ). Either inhibition of Aβ generation or enhancement of Aβ degradation is fundamental approach in developing effective ways to cure AD. We revealed that beta-secretase, which sheds beta-amyloid protein precursor (βAPP) to generate CTF-β, truncates Aβ at two sites. Interestingly, truncated Aβ aggregated much slower than full length Aβ, thus the truncation of Aβ by BACE may promote Aβ degradation. BACE may be utilized as Aβ degrading enzyme if the activity to shed βAPP is selectively inhibited somehow. Moreover, we showed that Aβ peptide inhibited BACE activity at least in vitro. This suggested that Aβ may inhibit BACE activity, which in turn reduces Aβ production. We propose that there might be negative feedback mechanism in Aβ generation cascade.
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Research Products
(18 results)
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[Journal Article] Presenilin-dependent γ-secretase on plasma membrane and endoso mes is functionally distinct2006
Author(s)
Fukumori A, Okochi M, Tagami S, Jiang J, Itoh N, Nakayama T, Yanagida K, Ishizuka-Katsura Y, Morihara T, Kamino K, Tanaka T, Kudo T, Tanii H, Ikuta A, Haass C, Takeda M
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Journal Title
Biochemistry 45
Pages: 5351-5358
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Presenilin-dependent γ-secretase on plasma membrane and endosomes is functionally distinct2006
Author(s)
Fukumori A, Okochi M, Tagami S, Jiang J, Itoh N, Nakayama T, Yanagida K, Ishizuka-Katsura Y, Morihara T, Kamino K, Tanaka T, Kudo T, Tanii H, Ikuta A, Haass C, Takeda M
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Journal Title
Biochemistry 45
Pages: 5351-5358
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Subcellular localization of γ-cleavage of βAPP.2004
Author(s)
Fukumori, A., Okochi, M., Jiang, J., Kimura, R., Tanii, H., Kudo, T., Tagami, S., Takeda, M
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The mechanism of intracellular amyloid beta degradation2004
Author(s)
Tagami, S., Okochi, M., Fukumori, A., Kimura, R., Jiang, J., Takeda, M
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Journal Title
9th International Conference on Alzheimer's Disease and Related Disorders Abstract Book 9巻
Pages: 97-97
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Biochemical separation of γ-cleavage of βAPP on the plasma membrane from that on the intracellular membrane2004
Author(s)
Fukumori, A., Okochi, M., Tagami, S, Tanii, H., Kimura, R., Jiang, J., Steiner, H., Haass, C., Kudo, T., Takeda, M.
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Journal Title
9th International Conference on Alzheimer's Disease and Related Disorders Abstract Book 9巻
Pages: 157-157
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The mechanism of intracellular amyloid beta degradation2004
Author(s)
Tagami, S., Okochi, M., Fukumori, A., Kimura, R., Jiang, J., Takeda, M
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Journal Title
9th International Conference on Alzheimer's Disease and Related Disorders Abstract Book 9
Pages: 97
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Biochemical separation of γ-cleavage of βAPP on the plasma membrane from that on the intracellular membrane2004
Author(s)
Fukumori, A., Okochi, M., Tagami, S., Tanii, H., Kimura, R., Jiang, J., Steiner, H., Haass, C., Kudo, T., Takeda, M.
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Journal Title
9th International Conference on Alzheimer's Disease and Related Disorders Abstract Book 9
Pages: 157
Description
「研究成果報告書概要(欧文)」より
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[Book] 痴呆とうつ 心療内科2005
Author(s)
田上真次, 大河内正康, 武田雅俊
Total Pages
402-407
Publisher
科学評論社
Description
「研究成果報告書概要(和文)」より
