Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3.
Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3.
复制标题
防止ataxin-3蛋白裂解可减轻SCA3果蝇模型中的变性。
DOI：
10.1093/hmg/ddp456
复制
发表时间：
2009-12-15
影响因子：
3.5
通讯作者：
Bonini NM
中科院分区：
文献类型：
--
作者：
Jung J;Xu K;Lessing D;Bonini NM
Protein cleavage is a common feature in human neurodegenerative disease. Ataxin-3 protein with an expanded polyglutamine (polyQ) repeat causes spinocerebellar ataxia type-3 (SCA3), also called Machado–Joseph disease, and is cleaved in mammalian cells, transgenic mice and SCA3 patient brain tissue. However, the pathological significance of Ataxin-3 cleavage has not been carefully examined. To gain insight into the significance of Ataxin-3 cleavage, we developed a Drosophila SL2 cell-based model as well as transgenic fly models. Our data indicate that Ataxin-3 protein cleavage is conserved in the fly and may be caspase-dependent as reported previously. Importantly, comparison of flies expressing either wild-type or caspase-site mutant proteins indicates that Ataxin-3 cleavage enhances neuronal loss in vivo. This genetic in vivo confirmation of the pathological role of Ataxin-3 cleavage indicates that therapies targeting Ataxin-3 cleavage might slow disease progression in SCA3 patients.
登录
查看更多内容
影响因子：
4.7
作者：
Hoffner, G;Island, ML;Djian, P
通讯作者：
Djian, P
影响因子：
64.5
作者：
Graham, Rona K.;Deng, Yu;Hayden, Michael R.
通讯作者：
Hayden, Michael R.
影响因子：
4.7
作者：
Berke, SJS;Schmied, FAF;Paulson, HL
通讯作者：
Paulson, HL
影响因子：
6.1
作者：
Pozzi, Chiara;Valtorta, Marco;Fusi, Paola
通讯作者：
Fusi, Paola
影响因子：
4.8
作者：
Winborn, Brett J.;Travis, Sue M.;Paulson, Henry L.
通讯作者：
Paulson, Henry L.