[Polyglutamine-expanded ataxin-3 is degraded by autophagy].
OBJECTIVE
To investigate the role of autophagy on the pathogenesis of spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD).


METHODS
HEK293 cells expressing polyglutamine-expanded ataxin-3 were used as cell model for SCA3/MJD. The level of polyglutamine-expanded ataxin-3 was detected after cells were treated with different inhibitors or inducer of autophagy.


RESULTS
Inhibition of autophagy increased aggregate formation and cell death in HEK293 cells expressing mutated ataxin-3, and vice versa.


CONCLUSIONS
The data suggested that autophagy is involved in the degradation of mutant ataxin-3, resulting in a decrease in the proportions of aggregate-containing cells and cell death in HEK293 cells expressing polyglutamine-expanded ataxin-3. It is possible that autophagy may be applied as a potential therapeutic approach for SCA3/MJD.
Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011 P.R.China.
Han
H
Xiao
Jianguang
J
Tang
Zhiping
Z
Hu
Jieqiong
J
Tan
Beisha
B
Tang
Zheng
Z
Jiang
D000067699:Ataxin-3; D001343:Autophagy; D002460:Cell Line; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3