Unknown

Dataset Information

0

Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3.


ABSTRACT: 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.

SUBMITTER: Jung J 

PROVIDER: S-EPMC2778376 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila model of SCA3.

Jung Joonil J   Xu Kexiang K   Lessing Derek D   Bonini Nancy M NM  

Human molecular genetics 20090925 24


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 a  ...[more]

Similar Datasets

| S-EPMC3764203 | biostudies-literature
| S-EPMC2574630 | biostudies-other
| S-EPMC1782370 | biostudies-literature
| S-EPMC8649108 | biostudies-literature
| S-EPMC6672614 | biostudies-literature
| S-EPMC8977414 | biostudies-literature
| S-EPMC2323314 | biostudies-literature
| S-EPMC7485683 | biostudies-literature
| S-EPMC6031360 | biostudies-literature
| S-EPMC10605626 | biostudies-literature