Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12)

Yu Chun Wang, Chi Mei Lee, Li Ching Lee, Li Chu Tung, Hsiu Mei Hsieh-Li, Guey Jen Lee-Chen, Ming Tsan Su*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

41 引文 斯高帕斯(Scopus)

摘要

Spinal cerebellar ataxia type 12 (SCA12) has been attributed to the elevated expression of ppp2r2b. To better elucidate the pathomechanism of the neuronal disorder and to search for a pharmacological treatment, Drosophila models of SCA12 were generated by overexpression of a human ppp2r2b and its Drosophila homolog tws. Ectopic expression of ppp2r2b or tws caused various pathological features, including neurodegeneration, apoptosis, and shortened life span. More detailed analysis revealed that elevated ppp2r2b and tws induced fission of mitochondria accompanied by increases in cytosolic reactive oxygen species (ROS), cytochrome c, and caspase 3 activity. Transmission electron microscopy revealed that fragmented mitochondria with disrupted cristae were engulfed by autophagosomes in photoreceptor neurons of flies overexpressing tws. Additionally, transgenic flies were more susceptible to oxidative injury induced by paraquat. By contrast, ectopic Drosophila Sod2 expression and antioxidant treatment reduced ROS and caspase 3 activity and extended the life span of the SCA12 fly model. In summary, our study demonstrates that oxidative stress induced by mitochondrial dysfunction plays a causal role in SCA12, and reduction of ROS is a potential therapeutic intervention for this neuropathy.

原文英語
頁(從 - 到)21742-21754
頁數13
期刊Journal of Biological Chemistry
286
發行號24
DOIs
出版狀態已發佈 - 2011 六月 17

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

指紋

深入研究「Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12)」主題。共同形成了獨特的指紋。

引用此