Research toward the development of a novel treatment for Parkinson disease by a moderate gene silencing with RNA interference.
Project/Area Number |
24390226
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | National Center of Neurology and Psychiatry |
Principal Investigator |
HOHJOH HIROHIKO 独立行政法人国立精神・神経医療研究センター, 神経研究所神経薬理研究部, 室長 (60238722)
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Co-Investigator(Kenkyū-buntansha) |
NAGAI Yoshitaka 独立行政法人国立精神, 神経医療研究センター・疾病研究第4部, 室長 (60335354)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
|
Keywords | RNAi / パーキンソン病 / α-シヌクレイン / 多重重複変異 / ショウジョウバエ / α‐シヌクレイン |
Outline of Final Research Achievements |
The alpha-synuclein (SNCA) gene is a responsible gene for Parkinson’s disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by an allele-specific RNAi; however, there is no method for restoring the SNCA overexpression to a normal level. In this study we showed that an atypical RNAi using siRNAs that confer a moderate level of gene silencing was capable of controlling overexpressed SNCA genes to return to a normal level; named ‘expression-control RNAi’ (ExCont-RNAi). To further assess its therapeutic effects, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as novel potentiator of cyclin-dependent kinases to enhance cell proliferation, independent of its hydrolase activity.2014
Author(s)
Kabuta T., Mitsui T., Takahashi M., Fujiwara Y., Kabuta C., Konya C., Tsuchiya Y., Hatanaka Y., Uchida K., Hohjoh H., and Wada K.
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Journal Title
J Biol Chem
Volume: 288
Pages: 12615-12626
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes.2013
Author(s)
Shin M., Ohte S., Fukuda T., Sasanuma H., Yoneyama K., Kokabu S., Miyamoto A., Tsukamoto S., Hohjoh H., Jimi E., and Katagiri T.
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Journal Title
J Bone Miner Metab
Volume: 31
Pages: 34-43
DOI
Related Report
Peer Reviewed
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[Journal Article] Pathogenic mutation of ALK2 inhibits iPS cell reprogramming and maintenance : mechanisms of reprogramming and strategy for drug identification.2012
Author(s)
Hamasaki M., Hashizume Y., Yamada Y., Katayama T., Hohjoh H., Fusaki N., Nakashima Y., Turuya H., Haga N., Takami Y., and Era T.
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Journal Title
Stem Cells
Volume: 30
Pages: 2437-2449
DOI
Related Report
Peer Reviewed
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