Therapeutics development against intellectual disability via structural biology analyses
Project/Area Number |
26640037
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Okazawa Hitoshi 東京医科歯科大学, 難治疾患研究所, 教授 (50261996)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | PQBP1 / スプライシング異常 / 構造生物学 / 遺伝子治療 / 小頭症 / 知的障害 / 神経変性疾患 / 神経変性 / 発達障害 / スプライシング / AIDS / HIV / 冠動脈疾患 / 天然変性タンパク質 / RNA / 機能障害 |
Outline of Final Research Achievements |
RNA splicing is implicated in the molecular pathology of neurological diseases, and the concept of RNA splicing diseases has been proposed. In this project, we focused on PQBP1, which is a representative RNA splicing disease gene, a representative disease gene of intellectual disability (ID), and a neurodegeneration-related gene. We intended to perform structural biology analysis of PQBP1 and develop revolutional therapy. As the results, we elucidated pathomechanisms of PQBP1-linked ID/microcephaly through splicing impairment, developed a gene therapy against this disorder. We also clarified structural basis of nteraction between PQBP1 and U5-15KD.
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain2016
Author(s)
Kamagata, K., Kerever, A., Yokosawa, S., Otake, Y., Ochi, H., Hori, M., Kamiya, K., Tsuruta, K., Tagawa, K., Okazawa, H., Aoki, S., Arikawa-Hirasawa, E.
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Journal Title
Magnetic Resonance in Medical Sciences
Volume: 15
Issue: 4
Pages: 416-421
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comprehensive phosphoproteome analysis unravels the core signaling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease brain.2015
Author(s)
Tagawa K, Homma H, Saito A, Fujita K, Chen X, Imoto S, Oka T, Ito H, Motoki K, Yoshida C, Hatsuta H, Murayama S, Iwatsubo T, Miyano S, Okazawa H.
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Journal Title
Hum Mol Genet.
Volume: 24
Issue: 2
Pages: 540-58
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells.2015
Author(s)
Ito H, Shiwaku H, Yoshida C, Homma H, Luo H, Chen X, Fujita K, Musante L, Fischer U, Frints SG, Romano C, Ikeuchi Y, Shimamura T, Imoto S, Miyano S, Muramatsu SI, Kawauchi T, Hoshino M, Sudol M, Arumughan A, Wanker EE, Rich T, Schwartz C, Matsuzaki F, Bonni A, Kalscheuer VM, Okazawa H.
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Journal Title
Mol Psychiatry
Volume: 20
Issue: 4
Pages: 459-71
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] HMGB1 facilitates repair of mitochondrial DNA damage and extends the lifespan of mutant ataxin-1 knock-in mice.2014
Author(s)
Ito H, Fujita K, Tagawa K, Chen X, Homma H, Sasabe T, Shimizu J, Shimizu S, Tamura T, Muramatsu S, Okazawa H.
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Journal Title
EMBO Mol Med.
Volume: 7
Issue: 1
Pages: 78-101
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mutations in the gene PQBP1 prevent its interaction with the spliceosomal protein U5-15kD2014
Author(s)
Mizuguchi, M., Obita, T., Serita, T., Kojima, R., Nabeshima, Y., and Okazawa, H.
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Journal Title
Nat Commun.
Volume: 5
Issue: 1
Pages: 3822-3822
DOI
Related Report
Peer Reviewed
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[Presentation] In utero treatment for PQBP-1 gene mutations2015
Author(s)
Hitoshi Okazawa
Organizer
10th International Meeting on Copy Number Variants and Genes in Intellectual Disability and Autism.
Place of Presentation
La Cittadella dell'Oasi (Troina, Italy)
Year and Date
2015-04-16
Related Report
Int'l Joint Research / Invited
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[Presentation] Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA12014
Author(s)
Tamura, T., Barclay, S, S., Fujita, K., Ito, H., Motoki, K., Shimamura, T., Tagawa, K., Katsuta, A., Shiwaku, H., Sone, M., Tagawa, K., Imoto, S., Miyano, S., Okazawa, H.
Organizer
Neuroscience2014
Place of Presentation
Yokohama
Year and Date
2014-09-11 – 2014-09-13
Related Report
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[Presentation] A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.2014
Author(s)
Fujita, K., Nakamura, Y., Oka, T., Ito, H., Tamura, T., Tagawa, K., Sasabe, T., Katsuta, A., Motoki, K., Shiwaku, H., Yoshida, C., Sone, M., Okazawa, H.
Organizer
Neuroscience2014
Place of Presentation
Yokohama
Year and Date
2014-09-11 – 2014-09-13
Related Report
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