| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Research Abstract |
To investigate the mechanisms of selective neuronal loss observed in the polyglutamine disease, we used Machado-Joseph disease (MJD) as a model for polyglutamine diseases. (1) We developed the polyclonal antibody raised against N-terminal side of ataxin-3 and immunohistochemically examined MJD brain with this antibody. In the MJD potine nucleus, soma of neurons and intranuclear inclusions were positively stained with anti-N-terminal ataxin-3 antibody, suggesting that intranuclear inclusions contain the epitope of N-terminal portion of ataxin-3. (2) Next, we investigate the aggregate formation and cytotoxicity produced by N-terminal truncated ataxin-3 (Q77) in different cultured cells (HeLa, Swiss3T3, P19, C2C12, COS-1, BHK-21, PC12, Neuro2a). Frequency of aggregates and cell death varies among different cell lines. Aggregate frequency was not correlated with that of cell death. Our results demonstrated that the differential susceptibility to death in various cell lines was evident even in the expression of N-terminal truncated ataxin-3 (Q77), suggesting that we do not need to hypothesize the presence of processing enzyme of ataxin-3 to explain the differential susceptibility.
|
