Generation of new mouse model for Parkinson's disease(Fostering Joint International Research)
Project/Area Number |
15KK0354
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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Allocation Type | Multi-year Fund |
Research Field |
Neurology
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Research Institution | Juntendo University |
Principal Investigator |
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Research Collaborator |
Sue Carolyn M シドニー大学, Kolling研究所・医学部, 教授
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Project Period (FY) |
2015 – 2017
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
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Keywords | パーキンソン病 / ミトコンドリア / CHCHD2 / 遺伝 / 呼吸鎖複合体 / 神経分化 / 解糖系 / ノックアウト細胞 / iPS細胞 / 活性酸素 / ATP / 酸化ストレス / 電子伝達系 / 遺伝子 |
Outline of Final Research Achievements |
We recently identified CHCHD2 mutations as a novel gene associated with autosomal dominant Parkinson’s disease (PD). CHCHD2 is localized to mitochondria and linked to mitochondrial complex IV function, however, its pathogenic mechanisms remain largely unknown. To elucidate the involvement between CHCHD2 and mitochondria, we generated CHCHD2-KO cells using CRISPR/Cas9 techniques, and performed mitochondrial phenotyping. Steady state ATP level and ATP synthesis rate were dramatically decreased in CHCHD2-KO cells. Steady state ATP level was partially rescued by overexpression of wildtype CHCHD2, but not by PD linked mutants of CHCHD2 (T61I and R145Q). Mitochondrial membrane potential, ROS, and superoxide were markedly and significantly increased in CHCHD2-KO cells. In conclusion, Loss of CHCHD2 impairs multiple mitochondrial functions and CHCHD2 KO cells may provide a useful cell model for understanding CHCHD2 function and pathophysiology of CHCHD2 mutations and PD.
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Report
(4 results)
Research Products
(18 results)
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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
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Peer Reviewed / Open Access
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[Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy.2018
Author(s)
Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
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Journal Title
J Neural Transm (Vienna)
Volume: -
Issue: 6
Pages: 938-944
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel mutation of CHCHD2 p.R8H in a sporadic case of Parkinson's disease2017
Author(s)
Ikeda, Aya; Matsushima, Takashi; Daida, Kensuke; Nakajima, Sho; Conedera, Silvio; Li, Yuanzhe; Yoshino, Hiroyo; Oyama, Genko; Funayama, Manabu; Nishioka, Kenya; Hattori, Nobutaka
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Journal Title
PARKINSONISM & RELATED DISORDERS
Volume: 34
Pages: 66-68
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of Parkinson's disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c.2017
Author(s)
Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Hatta T, Natsume T, Umitsu M, Takagi J, Imai Y, Hattori N.
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Journal Title
Nat Commun
Volume: 8
Issue: 1
Pages: 15500-15500
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication.2016
Author(s)
Takamura S, Ikeda A, Nishioka K, Furuya H, Tashiro M, Matsushima T, Li Y, Yoshino H, Funayama M, Morinobu S, Hattori N.
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Journal Title
Parkinsonism Relat Disord.
Volume: S1353-8020
Pages: 30028-1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lysosomal storage of subunit c of mitochondrial ATP synthase in brain-specific ATP13a2-deficient mice2016
Author(s)
Sato, S., Koike, M., Funayama, M., Ezaki, J., Fukuda, T., Ueno, T., Uchiyama, Y., Hattori, N
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Journal Title
Am. J. Pathol.
Volume: 186
Issue: 12
Pages: 3074-3082
DOI
Related Report
Peer Reviewed
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[Journal Article] Genotype-phenotype correlations of cysteine replacement in CADASIL.2016
Author(s)
Matsushima T, Conedera S, Tanaka R, Li Y, Yoshino H, Funayama M, Ikeda A, Hosaka Y, Okuzumi A, Shimada Y, Yamashiro K, Motoi Y, Nishioka K, Hattori N
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Journal Title
Neurobiology of Aging
Volume: 50
Related Report
Peer Reviewed
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[Presentation] A novel variant of CHCHD2 in a patient with sporadic Parkinson's disease.2017
Author(s)
Funayama M, Ikeda A, Matsushima T, Daida S, Nakajima S, Conedera S, Li Y, Yoshino H, Oyama G, Nishioka K, Hattori N
Organizer
日本人類遺伝学会第62階大会
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