IN VITRO CELLULAR MODEL FOR MACHADO-JOSEPH DESEASE, A MODEL FOR TRIPLET REPEAT DISEASES.
| Project/Area Number |
10670572
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
YOSHIZAWA Toshihiro ASSISTANT PROFESSOR DEPARTMENT OF NEUROLOGY, INSTITUTE OF CLINICAL MEDICINE, UNIVERSITY OF TSUKUBA, 臨床医学系, 講師 (50212311)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Machado-Joseph disease / polyglutamine / ataxin-3 / cell death / cell cycle / aggregation / neuron / マシャド・ジョセフ病 / ポリグルタシ鎖 |
|---|
| Research Abstract |
Machado-Joseph disease (MJD) is an inherited neurodegenerative disorder caused by the expansion of the polyglutamine stretch in the MJD-gene coding protein (ataxin-3). Using a series of deletion constructs expressing ataxin-3 fragments with the expanded polyglutamine stretch, we observed aggregate formation and cell death in the cultured BHK-21 cells. The cytotoxic effect of the N-terminal-truncated ataxin-3 with the expanded polyglutamine tract was enhanced under the serum-starved culture condition, in which the cells were arrested in the G0/G1 phase. Co-expression of p21ィイD1waf1/cip1/sdi1ィエD1, a cyclin-Cdk inhibitor, that induced cell cycle arrest in the G1 phase, also increased the susceptibility to cell death produced by the mutant ataxin-3 fragment in BHK-21 cells. Finally, the elevated susceptibility to cell death in the G0/G1 phase was confirmed in the nerve growth factor-treated, postmitotic neuronal PC12 cells compared to the undifferentiated proliferating PC12 cells. These results strongly suggest that the cellular toxicity of the truncated ataxin-3 with the expanded polyglutamine stretch is enhanced by cell cycle arrest in the G0/G1 phase. The mutant ataxin-3 may confer a higher susceptibility to cell death on the cells in the G0/G1 phase.
|
Report
(3 results)
Research Products
(7 results)
