Production mechanism and functional role of myelin protein produced by stop codon readthrough
Project/Area Number |
24500449
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Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Tokyo University of Pharmacy and Life Science |
Principal Investigator |
BABA Hiroko 東京薬科大学, 薬学部, 教授 (40271499)
|
Co-Investigator(Renkei-kenkyūsha) |
YAMAGUCHI Yoshihide 東京薬科大学, 薬学部, 准教授 (50311832)
HAYASHI Akiko 東京薬科大学, 薬学部, 講師 (90232090)
|
Research Collaborator |
NAKANISHI Hiroki
YANO Noriko
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | リードスルー / ミエリン / 細胞接着 / リン酸化 / PKC / 神経科学 / 翻訳 / 脳・神経 |
Outline of Final Research Achievements |
L-MPZ is a novel isoform of myelin P0 that is produced from P0 mRNA by stop codon readthrough mechanism. Antibodies against L-MPZ are often found in the patient sera with peripheral neuropathy, but the role of the antibodies in neuropathy is unknown. In present study, production mechanism, function of L-MPZ in myelin, and relevance of the antibody to demyelination were examined. We found that rate of L-MPZ production (ratio of L-MPZ/P0) was dependent on the nucleotide sequence near the stop codon, and readthrough stimulating drug, G418, significantly elevated this ratio. L-MPZ showed cell adhesion activity in the transfected cells. Anti-L-MPZ antibody did not induce demyelination, but further study on its role in remyelination may be needed. Since cell adhesion activity of L-MPZ was weaker than that of P0, change of L-MPZ/P0 ratio may affect adherence of myelin layers. Thus, our study suggests that precausion should be needed when readthrough stimulating drugs are used for therapy.
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Report
(4 results)
Research Products
(12 results)