2007 Fiscal Year Final Research Report Summary
The elucidation of onset mechanism of Alzheimer's disease.
| Project/Area Number |
18590355
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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 |
Human pathology
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
ISHIGAMI Akihito Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Senior research scientist (50270658)
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| Co-Investigator(Kenkyū-buntansha) |
HANDA Setsuko Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, 東京都老人総合研究所, Research Assistant (30360697)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Alzheimer's disease / neurodegenerative disorder / citrullinated protein / neuron / astrocyte / apoptosis / calcium / arginine |
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| Research Abstract |
Citrullinated proteins are the products of a post-translational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and functions. In mammalian tissues, PADs are found as five different isoforms (i.e, types 1-4, 6). PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of the citrullination in neuronal degeneration, we examined whether citrullinated proteins are produced in Alzheimer's disease (AD), Parkinson's disease, and Huntington chorea.
1. Histochemical analysis revealed that citrullinated proteins were detected all over the hippocampus. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also detected all over the hippocampus both in the AD and the normal brain. Double immunofluorescence staining revealed that citrullinated protein-and PAD2-positive cells were well coincidenced with GFAP-positive cells, but not all GFAP-positive cells were PAD2-positive cells. As GFAP is a astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes.
2. Citrullinated proteins with various molecular weight were detected in AD hippocampus by Western blot analysis, but not in normal brain. Two of the citrullinated proteins were identified as a vimentin and a glial fibrillary acidic protein (GFAP).
Thus, abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 is occurring in AD hippocampus. These results strongly suggested that PAD has an important role in the onset and progression of AD and citrullinated proteins may became a possible useful marker for human neurodegenerative disease.
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[Journal Article] Hepatoprotective effect of Arazyme on CCl_4-induced acute hepatic injury in SMP30 knock-out mice.2008
Author(s)
Park, JK., Jeong, DH., Park, HY., Son, KH., Shin, DH., Do, SH., Yang, HJ., Yuan, DW., Hong, IH., Goo, MJ., Lee, HR., Ki, MR., Ishigami A., and Jeong, KS.
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Journal Title
Toxicology 256
Pages: 132-142
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Senescence Marker Protein 30 Functions as Gluconolactonase in L-Ascorbic Acid Biosynthesis and Its Knockout Mice Are Prone to Scurvy.2006
Author(s)
Kondo, Y., Inai, Y., Sato, Y., Handa, S., Kubo, S., Shimokado, K., Goto, S., Nishikimi, M., Maruyama, N., and Ishigami, A.
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Journal Title
Proc. Nat. Acad. Sci. USA 103
Pages: 5723-5728
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Senescence Marker Protein-30 Protects Mice Lungs from Oxidative Stress, Aging and Smoking2006
Author(s)
Sato, T., Seyama, K., Sato, Y., Mon, H., Souma, S., Akiyoshi, T., Kodama, Y., Mori, T., Goto, S., Takahashi, K., Fukuchi, Y., Maruyama, N., and Ishigami, A.
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Journal Title
Am. J. Respir. Crit. Care Med 174
Pages: 530-237
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The increased protein oxidation and the altered expression of Ca^<2+> regulatory proteins in senescence marker protein 30 deficient brain.2006
Author(s)
Son, T.G., Zou, Y., Jung, K.J., Je, J.H., Yu, B.P., Ishigami, A., Maruyama, N. and Lee, J.
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Journal Title
Mech. Aging Dev. 127
Pages: 451-457
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Accelerated tubular cell senescence in SMP30 knockout mice.2006
Author(s)
Yumura, W., Imasawa, T., Suganuma, S., Ishigami. A., Handa, S., Kubo, S. and Maruyama, N.
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Journal Title
Histol. Histopathol. 21
Pages: 1151-1156
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A selective NFkappaB inhibitor, DHMEQ, reduced atherosclerosis in apoE-deficient mice.2006
Author(s)
Chiba, T., Kondo, Y., Shinozaki, S., Kaneko, E., Ishigami, A., Maruyama, N., Umezawa, K. and Shimokado, K.
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Journal Title
J. Atheroscler Thromb. 6
Pages: 308-313
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Increased citrullinated proteins in the brains of scrarpie-infected mice.2006
Author(s)
Jang, B., Kim, E., Choi, JK., Jin, JK., Ishigami, A., Choi, EK.
Organizer
2006 Conference of the Korea Society for Gerontology and Institute of Pharmaceutical Science
Place of Presentation
Kangwon National University, Chuncheon, Korea
Year and Date
2006-06-22
Description
「研究成果報告書概要(欧文)」より
