On the transneuronal propagation in neurodegenerative diseases
| Project/Area Number |
15K06754
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柿田 明美 新潟大学, 脳研究所, 教授 (80281012)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 神経変性疾患 / 筋萎縮性側索硬化症 / パーキンソン認知症 / グアム / リン酸化タウ / リン酸化TDP-43 / 病変ステージ / 伝播 / パーキンソン－認知症 / ALS / 軸索 / TDP-43 / プリオン仮説 |
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| Outline of Final Research Achievements |
Phosphorylated (p-) TDP-43 inclusions were frequently observed in the axons of the lower motoneurons of 19 autopsy cases with amyotrophic lateral sclerosis (ALS). The forms of the inclusions were granuloreticular and massive aggregate types. Presynaptic p-TDP-43 inclusions were observed around the neurons of the red nucleus, however, postsynaptic p-TDP-43 aggregates were not seen. The finding showed transsynaptic p-TDP-43 propagation was not examined in the ALS patients. Stages of brain lesions by phosphorylated tau-immunohistochemistry in the Guam PDC, Guam ALS and Guam controls were identified five (0 - IV). Differences from those of Alzheimer’s disease were massive progression into brainstem and rare neuropile threads.
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病（AD），筋萎縮性側索硬化症（ALS），前頭側頭葉変性症，パーキンソン病などのレビー小体病，グアム島のパーキンソン認知症（G-PDC）などは原因不明で根本的治療法が無い致死性の疾患である。これらの疾患は特異的蛋白が脳脊髄に発現して伝播拡散し沈着することで発症する。これらの変性疾患を予防および治療するには、それぞれの特異蛋白がどのようにして神経組織に発現し拡散伝播するのか、そのメカニズムを解明することが重要である。本研究はALSの脳脊髄におけるリン酸化TDP-43の軸索内所見を初めて明らかにし、G-PDCのリン酸化タウの進展様式がADとは異なることを見出し報告した。
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Report
(5 results)
Research Products
(23 results)
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[Journal Article] Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.2016
Author(s)
Oyanagi K, Kinoshita M, Suzuki-Kouyama E, Inoue T, Nakahara A, Tokiwai M, Arai N, Satoh JI, Aoki N, Jinnai K, Yazawa I, Arai K, Ishihara K, Kawamura M, Ishizawa K, Hasegawa K, Yagisita S, Amano N, Yoshida K, Terada S, Yoshida M, Akiyama H, Mitsuyama Y, Ikeda SI.
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Journal Title
Brain Pathol.
Volume: 印刷中
Issue: 6
Pages: 748-769
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis2016
Author(s)
Onozato T, Nakahara A, Suzuki-Kouyama E, Hineno A, Yasude T, Nakamura T, Yahikozawa H, Watanabe M, Kayanuma K, Makishita H, Ohara S, Hashimoto T, Higuchi K, Sakai T, Asano K, Hashimoto T, Kanno H, Nakayama J, Oyanagi K
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Journal Title
Neuropathol Appl Neurobioly
Volume: 42
Pages: 561-572
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis2016
Author(s)
Onozato T, Nakahara A, Suzuki-Kouyama E, Hineno A, Yasude T, Nakamura T, Yahikozawa H, Watanabe M, Kayanuma K, Makishita H, Ohara S, Hashimoto T, Higuchi K, Sakai T, Asano K, Hashimoto T, Kanno H, Nakayama J, Oyanagi K
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Journal Title
Neuropathology and Applied Neurobioly
Volume: 印刷中
Issue: 6
Pages: 561-572
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Predictors of impaired communication in amyotrophic lateral sclerosis patients with tracheostomy invasive ventilation2015
Author(s)
Nakayama Y, Shimizu T, Mochizuki Y, Hayashi Y, Matsuda C, Nagao M, Watabe K, Kawata A, Oyanagi K, Isozaki E, Nakano I
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Journal Title
Amyotroph Lateral Scler Frontotemporal Degener
Volume: 未
Issue: 1-2
Pages: 38-46
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets2017
Author(s)
Oyanagi K, Kinoshita M, Nakahara A, Satoh J, Aoki N, Jinnai K, Yazawa I, Arai K, Ishihara K, Kawamura M, Arai N, Hasegawa K, Yagishita S, Amano N, Yoshida K, Terada S, Yoshida M, Akiyama H, Mitsuyama Y, Ikeda S
Organizer
XXIII World Congress of Neurology
Related Report
Int'l Joint Research
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