Investigation of Parkinsonism by PKC pathway disruption and application for the new treatment for Parkinon's disease
Project/Area Number |
16K19019
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
General pharmacology
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Research Institution | Hiroshima University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | PKC / パーキンソン病 / リン酸化 / CSPalpha / HPS70 / CSP alpha / プロテオーム / プレシナプス |
Outline of Final Research Achievements |
We focused on cysteine string protein alpha (CSPa), one of HSP40 localized on synaptic vesicles. We found that PKCg phosphorylates CSPa at Serine10 and Ser34. Apoptosis was found to have been enhanced by the overexpression of a phosphorylation null mutant of CSPa, CSPa(S10A/S34A). The CSPa(S10A/S34A) mutant had a weaker interaction with HSP70 than WT CSPa, but a phosphomimetic CSPa(S10D/S34D) mutant had a stronger interaction with HSP70 than WT CSPa. Total levels of SNAP25, a main downstream of the HSP70 chaperone complex, was found to have decreased by the CSPa(S10A/S34A) mutant, through increased ubiquitination of SNAP25 in PC12 cells. In the striatum of 2-year-old PKCg KO mice, decreased phosphorylation levels of CSPa and decreased SNAP25 protein levels were observed. These findings indicate the phosphorylation of CSPa by PKCg may protect the presynaptic terminal from neurodegeneration. The PKCg-CSPa-HSP70-SNAP25 axis may provide a new therapeutic target for the treatment of PD.
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Validation of Anti-CSPα, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting.2018
Author(s)
Shirafuji T, Ueyama T, Tanaka S, Hide I, Saito N, Sakai N.
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Journal Title
Acta Histochem Cytochem.
Volume: 50 (6)
Pages: 177-180
NAID
Related Report
Peer Reviewed
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[Journal Article] The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance.2018
Author(s)
Shirafuji T, Ueyama T, Adachi N, Yoshino KI, Sotomaru Y, Uwada J, Kaneoka A, Ueda T, Tanaka S, Hide I, Saito N, Sakai N.
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Journal Title
J Neurosci.
Volume: 38 (2)
Pages: 278-290
Related Report
Peer Reviewed
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