Towards a comprehensive understanding of molecular pathogenesis for amyotrophic lateral sclerosis
| Project/Area Number |
23300129
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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| Keywords | 脳神経疾患 / 脳・神経 / 遺伝子 / 蛋白質 / 動物 / 筋萎縮性側索硬化症 / オートファジー / 酸化ストレス / マウスモデル / SOD1 / ALS2 / p62/SQSTM1 / Nrf2 |
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| Research Abstract |
Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Although multiple toxicity pathways including oxidative stress, neural inflammation, protein misfolding and accumulation, and dysfunctional intracellular trafficking, are implicated in the pathogenesis of ALS, molecular basis of the interplay between such multiple factors are largely unknown. To address this issue, we investigate a role of GFAP, Nrf2, ALS2, and p62/SQSTM1 , and their interrelationship in the onset and progression of ALS using mutant SOD1-expressing ALS mouse models. The results indicate that loss of either ALS2 or p62/SQSTM1 exacerbates motor dysfunction in ALS mice. Importantly, a simultaneous inactivation of ALS2 and p62/SQSTM1 in ALS mice further accelerates the disease phenotypes. Thus, dysfunction in the autophagy-endolysosomal system might play a crucial role in motor neuron degeneration.
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Report
(4 results)
Research Products
(80 results)
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[Journal Article] SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis.2014
Author(s)
Chen, Y. P., Zheng, Z. Z., Chen, X. P., Huang, R., Yang, Y., Yuan, L. X., Pan, L., Hadano, S., and Shang, H. -F.
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Journal Title
Neurobiol. Aging
Volume: 35
Issue: 3
Pages: 726.e7-726.e9
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel small-molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2 -(2,4,6-trimethylphenoxy)acetamide, selectively protects against oxidative stress-induced cell death by activating the Nrf2-ARE pathway : Therapeutic implications for ALS2012
Author(s)
Kanno T, Tanaka K, Yanagisawa Y, Yasutake K, Hadano S, Yoshii F, Hirayama N, and Ikeda J. E
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Journal Title
Free Radical Biol. Med
Volume: 53(11)
Pages: 2028-2042
Related Report
Peer Reviewed
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[Presentation] オートファジー関連因子p62/SQSTM1 の機能喪失はALS マウスモデルの疾患症状を悪化させる2014
Author(s)
秦野伸二, 潘雷, 大友麻子, 阿部幸一郎, 小池正人, 内山安男, 青木正志, 吉井文均, 石井哲郎, 柳川徹
Organizer
日本実験動物科学技術さっぽろ2014 : 第61回日本実験動物学会総会/第48回日本実験動物技術者協会総会
Place of Presentation
札幌(講演要旨集, p190(O088-S))
Related Report
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[Presentation] Loss of p62/SQSTM1 exacerbates motor dysfunction in a mutant SOD1-expressing mouse ALS model2013
Author(s)
Pan L, Otomo A, Abe K, Ogawa H, Chiba T, Koike M, Uchiyama Y, Aoki M, Yoshii F, Ishii T, Yanagawa T, Hadano S
Organizer
24th International Symposium on ALS/MND
Place of Presentation
Milan, Italy(Amyotroph. Lateral Scler. Frontotempo. Degen. 14 (suppl. 1), 180-181 (P217))
Related Report
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[Presentation] Inositol hexakisphosphate kinase 2 is one of the candidate molecules as diagnostic marker for amyotrophic lateral sclerosis2013
Author(s)
Nagata E, Moriya Y, Fujii N, Kohara S, Satoh T, Takao M, Pan L, Ogawa H, Hadano S, Mihara B, Takizawa S
Organizer
Neuro2013 : 第36回日本神経科学会大会/第56回日本神経化学会大会/第23回日本神経回路学会大会
Place of Presentation
京都(O2-9-1-1)
Related Report
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[Presentation] Loss of p62/SQSTM1 exacerbates motor dysfunction in a mutant SOD1-expressing mouse ALS model.2013
Author(s)
Pan, L., Otomo, A., Abe, K., Ogawa, H., Chiba, T., Koike, M., Uchiyama, Y., Aoki, M., Yoshii, F., Ishii, T., Yanagawa, T., and Hadano, S.
Organizer
24th International Symposium on ALS/MND
Place of Presentation
Milan, Italy
Related Report
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[Presentation] SQSTM1 mutations in sporadic Chinese patients with amyotrophic lateral sclerosis.2013
Author(s)
Chen, Y., Chen, X., Huang, R., Zheng, Z., Wei, Q., Guo, X., Pan, L., Hadano, S., and Shang, H.
Organizer
24th International Symposium on ALS/MND
Place of Presentation
Milan, Italy
Related Report
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[Presentation] Different human copper-zinc superoxide dismutase mutants, SOD1^<G93A> and SOD1^<H46R>, exert distinct harmful effects on gross phenotype in mice2012
Author(s)
Pan L, Yoshii Y, Otomo A, Ogawa H, Iwasaki Y, Shang H. F and Hadano S
Organizer
23rd International Symposium on ALS/MND
Place of Presentation
Chicago, Illinois, U.S.A.(Amyotroph. Lateral Scler. 13 (suppl. 1), 36 (C60))
Related Report
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[Presentation] Role of inositol hexakisphosphate kinase 2 in a mouse model for amyotrophic lateral sclerosis2012
Author(s)
Moriya, Y., Nagata, E., Pan, L Sato T, Ogawa H, Hadano S, Takizawa S
Organizer
Neuroscience 2012
Place of Presentation
New Orleans, Louisiana, U.S.A(Program#/Poster#: 242.06/E24)
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