Pathogenesis of Alzheimer's disease by aberrant APP transport
Project/Area Number |
20390018
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Hokkaido University |
Principal Investigator |
SUZUKI Toshiharu Hokkaido University, 大学院・薬学研究院, 教授 (80179233)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
|
Keywords | アルツハイマー病 / APP / 小胞輸送 / キネシン / 神経 / 神経変性疾患 / βアミロイド / アミロイド前駆体タンパク質 / キネシンモーター / 膜小胞輸送 / 微小管 / タンパク質リン酸化 / 神経細胞 / 軸索順行輸送 / 老化 / アルカデイン / JIP / セクレターゼ |
Research Abstract |
Major cause of Alzheimer's disease is production of β-amyloid (Aβ) and neurotoxic oligomer formation of Aβ. Aβ is a metabolic product generated by cleavage of the amyloid β-protein precursor (APP) by the successive action of β- and γ-secretases. Mutation in the presenilin component of γ-secretase can cause alternative intramembrane processing of APP, leading to aberrant speciation of Aβ, which, in turn, can lead to familial AD (FAD). In contrast to FAD, the primary cause of sporadic type of AD remains unclear. Several membrane and trnasmembrane proteins have been associated with AD, and the disruption of the vesicular transport system is observed in AD brains, suggesting that defects in the membrane trafficking system, including axonal vesicular transport, may be a primitive cause of AD pathogenesis. I focused this research on the analysis of APP vesicular trafficking. APP is known to cargo-receptor of kinesin-1. Our previous studies revealed that APP is associated to KLC through JIP1 mediation. Furthermore, disruption of APP vesicular transprort increased the generation of neurotoxic Aβ. However, the molecular mechanism how APP and kinesin-1 association is regulated remains unclear in detail. We revealed the association between JIP1 and KLC in detail and proposed how the association is regulated.
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Report
(4 results)
Research Products
(127 results)
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[Journal Article] Phosphorylation the amino-terminal : region of X11L regulates its intera ction with APP2009
Author(s)
Sakuma, M., Tanaka, E., Taru, H., Tomita, S., Gandy, S., Nairn, A. C., Nakaya, T., Yamamoto, T. and Suzuki, T.
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Journal Title
Journal of Neurochemistry (In press)Feb.14Epub
Related Report
Peer Reviewed
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[Journal Article] Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation.2009
Author(s)
Guix, F. X., Ill-Raga, G., Bravo, R., Nakaya, T., de Fabritiis, G., Coma, M., Miscione, G. P., Villa-Freixa, J., Suzuki, T., Fer nandez-Busquets, X., Valverde, M. A., de Strooper, B. and Mu. noz, F. J.
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Journal Title
Brain (In press)Feb.27Epub
Related Report
Peer Reviewed
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[Journal Article] X11 proteins regulate the translocation of APP into detergent resistant membrane and suppress the amyloidogenic cleavage of APP by BACE in brain.2008
Author(s)
Saito, Y., Sano, Y., Vassar, R., Gandy, S., Nakaya, T., Yamamoto, T., and Suzuki, T.
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Journal Title
Journal of Biological Chemistry 283
Pages: 35763-35771
Related Report
Peer Reviewed
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[Journal Article] X11L / X11β / MINT2 and X11L2 / X11γ / MINT3 scaffold proteins shutfle between the nucleus and cytoplasm2008
Author(s)
Sumioka, A., Saito, Y., Sakuma, M., Araki, T., Yamamoto, T. and Suzuki, T.
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Journal Title
Experimental Cell Research 314
Pages: 1155-1162
Related Report
Peer Reviewed
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[Presentation] Analysis of Alcadein Metabolic Fragments in Brain2008
Author(s)
○Araseki, M., Hata, S., Nakaya, T., Gandy S., Martins, R.N., Suzuki, T.
Organizer
Alzheimer's Association ICAD 2008
Place of Presentation
Chicago USA McCormick Place
Related Report
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[Presentation] Intracellular dynamics of Alcadein family molecules and their metabolites in neuronal cells and tissues2008
Author(s)
○Gotoh, N., Uralio, S., Maruta, C., Nakaya, T., Suzuki, T. and Yamamoto, T.
Organizer
Alzheimer's Association ICAD 2008
Place of Presentation
Chicago USA Chicago USA
Related Report
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[Presentation] Analysis of axonal transport of APP in JIP1 gene-deficient mice2008
Author(s)
○Furukori, K., Araki, Y., Taru, H., Yamamoto, T., Davis, R. J., and Suzuki, T.
Organizer
Alzheimer's Association ICAD 2008
Place of Presentation
Chicago USA McCormick Place
Related Report
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[Presentation] Analysis of β-Alc : Alcadein processing yield fragment homologous to APP P3 peptide2008
Author(s)
○Hata, S., Araki, Y., U rakami, K., Akatsu, H., Nishimura, M., Gandy, S., Nakaya, T. and Suzuki, T.
Organizer
Alzheimer's Association ICAD 2008
Place of Presentation
Chicago USA McCormick Place
Related Report
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