Pro-apoptotic protein GAPDH: Implication in the pathogenesis of Parkison's disease
| Project/Area Number |
13672295
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Josai University |
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Principal Investigator |
ISHITANI Ryoichi Josai University, Group on Cellular Neurobiology, Professor, 薬学部, 教授 (80077958)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIYA Katusmi Josai University, Group on Cellular Neurobiology, Associate Professor, 薬学部, 助教授 (80095314)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Neuronal death / Apoptosis / GAPDH / Parkison's disease / Lewy body / Neurodegenerative disorders / GAPDH promoter |
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| Research Abstract |
It is now apparent that a protein, referred to as pro-apoptotic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), with a quite mundane function in healthy cells behaves very differently during cell suicide. Our recent findings demonstrated that the overexpression of GAPDH prior to neuronal death is critically regulated at the promoter region, and the respective functional domains control both signals for subsequent aggregate formation and nuclear translocation of this protein. Furthermore, the immunocreative profiles of GAPDH nuclear aggregates could be detected in the post-mortem brains of Machado-Joseph disease, dentatorubral-pallidoluysian atrophy, Parkison's disease (PD), and Alzheimer's disease (AD) patients. Abnormal folding and aggregation of proteins has been extensively explored as one of the central mechanisms leading to neurodegeneration in disorders such as AD, PD, and CAG repeat diseases. In PD, α-synuclein accumulates in insoluble inclusions and various factors promote this aggregation. To clarify the possible role of pro-apoptotic protein GAPDH as a stimulator of α-synuclein aggregation in PD, we performed co-transfection studies on COS-7 cells. We found that: (1) co-transfection of α-synuclein (wild-type & A53T) with GAPDH yields cytoplasmic Lewy body-like inclusions, while β-synuclein is less effective, (2) GAPDH and α-synuclein co-immunoprecipitate in transfected cells, (3) particularly perinuclear inclusions are thioflavin S-positive, suggesting the amyloid-like coformation, and (4) an antibody to the pro-apoptotic protein GAPDH distinctly stains the core region in Lewy bodies of the PD post-mortem subjects. These findings suggest the involvment of pro-apoptotic protein GAPDH in the pathogenesis of PD through promoting an aggregation of α-synuclein during apoptotic death pathway.
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Report
(3 results)
Research Products
(10 results)
