Elucidation of the mechanisms of the Parkinson's disease genes and Lewy Body formation and alpha-synuclein propagation mechanisms
Project/Area Number |
18H04043
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Medium-sized Section 52:General internal medicine and related fields
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Research Institution | Juntendo University |
Principal Investigator |
Hattori Nobutaka 順天堂大学, 医学(系)研究科(研究院), 教授 (80218510)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2020: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
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Keywords | パーキンソン病 / α-シヌクレイン / SNCA / Lewy小体 / ミトコンドリア / オートファジー / CHCHD2 / PLA2G6 / レヴィ小体 / SNCA / 遺伝性パーキンソン病 / α-synuclein / 脂質組成 / 遺伝子解析 / 神経細胞死 / 伝播形式 |
Outline of Final Research Achievements |
In models of CHCHD2 knockout flies, knockout mice, and patient-derived iPS cells, mitochondrial function declines in an age-dependent manner, forming SNCA-positive Lewy body-like inclusion bodies. Furthermore, analysis of PLA2G6 knockout flies showed shortening of the acyl group of brain phospholipids. It was clarified that the homeostasis of mitochondrial protein and phospholipid composition is the primary cause of the mechanism of aggregate formation in Parkinson's disease.
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Academic Significance and Societal Importance of the Research Achievements |
封入体を形成する遺伝性パーキンソン病に着目し、モデル動物の解析により封入体形成のメカニズム解明に迫ることができた。本研究の成果は多くを占める孤発性パーキンソン病の病態解明につながるものであり、今後の疾患予防や治療法開発に向けて基礎的な知見となる。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Variants in saposin D domain of prosaposin gene linked to Parkinson’s disease2020
Author(s)
Oji Y, Hatano T, Ueno SI, Funayama M, Ishikawa KI, Okuzumi A, Noda S, Sato S, Satake W, Toda T, Li Y, Hino-Takai T, Kakuta S, Tsunemi T, Yoshino H, Nishioka K, Hattori T, Mizutani Y, Mutoh T, Yokochi F, et al.
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Journal Title
Brain
Volume: 143
Issue: 4
Pages: 1190-1205
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pathological findings in a patient with alpha-synuclein p.A53T and familial Parkinson's disease2020
Author(s)
Nishioka K, Hashizume Y, Takanashi M, Daida K, Li Y, Yoshino H, Tambasco N, Prontera P, Hattori Y, Ueda A, Watanabe H, Hattori N.
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Journal Title
Parkinsonism and related disorders
Volume: In press
Pages: 183-187
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Nonmercaptalbumin as an oxidative stress marker in Parkinson's and PARK2 disease2020
Author(s)
Ueno SI, Hatano T, Okuzumi A, Saiki S, Oji Y, Mori A, Koinuma T, Fujimaki M, Takeshige-Amano H, Kondo A, Yoshikawa N, Nojiri T, Kurano M, Yasukawa K, Yatomi Y, Ikeda H, Hattori N
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Journal Title
Ann Clin Transl Neurol
Volume: 7
Issue: 3
Pages: 307-317
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Neuromelanin or DaT-SPECT: which is the better marker for discriminating advanced Parkinson's disease?2019
Author(s)
Okuzumi A, Hatano T, Kamagata K, Hori M, Mori A, Oji Y, Taniguchi D, Daida K, Shimo Y, Yanagisawa N, Nojiri S, Aoki S, Hattori N
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Journal Title
Eur J Neurol
Volume: 26
Issue: 11
Pages: 1408-1416
DOI
Related Report
Peer Reviewed
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[Journal Article] Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling.2019
Author(s)
Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 116(41)
Issue: 41
Pages: 20689-20699
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mutations in CHCHD2 cause α-synuclein aggregation2019
Author(s)
Ikeda A., Nishioka K., Meng H., Takanashi M., Hasegawa I., Inoshita T., Shiba-Fukushima K., Li Y., Yoshino H., Mori A., Okuzumi A., Yamaguchi A., Nonaka R., Izawa N., Ishikawa K.I., Saiki H., Morita M., Hasegawa M., Hasegawa K., Elahi M., et al.
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Journal Title
Human Molecular Genetics
Volume: 28
Issue: 23
Pages: 3895-3911
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Metabolomics‐based identification of metabolic alterations in PARK22019
Author(s)
Okuzumi Ayami、Hatano Taku、Ueno Shin‐Ichi、Ogawa Takashi、Saiki Shinji、Mori Akio、Koinuma Takahiro、Oji Yutaka、Ishikawa Kei‐Ichi、Fujimaki Motoki、Sato Shigeto、Ramamoorthy Sivapriya、Mohney Robert P.、Hattori Nobutaka
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Journal Title
Annals of Clinical and Translational Neurology
Volume: 6
Issue: 3
Pages: 525-536
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson's Disease.2018
Author(s)
Ueno SI, Saiki S, Fujimaki M, Takeshige-Amano H, Hatano T, Oyama G, Ishikawa KI, Yamguchi A, Nojiri S, Akamatsu W, Hattori N.
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Journal Title
Cells
Volume: 8
Issue: 1
Pages: 14-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease.2018
Author(s)
Fujimaki M, Saiki S, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N.
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Journal Title
Neurology.
Volume: 90
Issue: 5
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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