Neural Regeneration Research ›› 2015, Vol. 10 ›› Issue (8): 1286-1291.doi: 10.4103/1673-5374.162763

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The E3 ubiquitin ligase seven in absentia homolog 1 may be a potential new therapeutic target for Parkinson’s disease

Zeng-lin Cai1,  Jing Xu1, Shou-ru Xue2, Yuan-yuan Liu2, Yong-jin Zhang1, Xin-zhi Zhang1, Xuan Wang1, Fang-ping Wu1, Xiao-min Li1   

  1. 1 Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China
    2 Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China  
  • Received:2015-06-09 Online:2015-08-24 Published:2015-08-24
  • Contact: Zeng-lin Cai, M.D., Jing Xu, Ph.D. or hou-ru Xue, M.D., caizengling@hotmail.com, 369610503@qq.com or xueshouru@suda.edu.cn.
  • Supported by:

    This study was supported by the China Postdoctoral Science Foundation, No. 1630; the Natural Science Foundation of Jiangsu Province in China, No. BK2011402; the Jiangsu Province Postdoctoral Research Foundation in China, No. 1301174C; the Jiangsu Province Health Department Foundation in China, No. H201361.

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Abstract:

In this study, we investigated the effect of an antibody against E3 ubiquitin ligase seven in absentia homolog 1 (SIAH-1) in PC12 cells. 1-Methyl-4-phenylpyridinium (MPP+) treatment increased α-synuclein, E1 and SIAH-1 protein levels in PC12 cells, and it reduced cell viability; however, there was no significant change in light chain 3 expression. Treatment with an SIAH-1 antibody decreased mRNA expression levels of α-synuclein, light chain 3 and SIAH-1, but increased E1 mRNA expression. It also increased cell viability. Combined treatment with MPP+ and rapamycin reduced SIAH-1 and α-synuclein levels. Treatment with SIAH-1 antibody alone diminished α-synuclein immunoreactivity in PC12 cells, and reduced the colocalization of α-synuclein and light chain 3. These findings suggest that the SIAH-1 antibody reduces the monoubiquitination and aggregation of α-synuclein, promoting its degradation by the ubiquitin-proteasome pathway. Consequently, SIAH-1 may be a potential new therapeutic target for Parkinson’s disease.

Key words: nerve regeneration, neurodegeneration, Parkinson’s disease, ubiquitin-proteasome system, autophagy, E3 ubiquitin ligase seven in absentia homolog 1, 1-methyl-4-phenylpyridinium, rapamycin, neural regeneration