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

• Published in: Neural regeneration research 2015-01, Vol.10 (8), p.1286-1291
• Main Authors: Cai, Zeng-lin, Xu, Jing, Xue, Shou-ru, Liu, Yuan-yuan, Zhang, Yong-jin, Zhang, Xin-zhi, Wang, Xuan, Wu, Fang-ping, Li, Xiao-min
• Format: Article
• Language: English
• Subjects: Autophagy; Biotechnology; Infrared imaging systems; 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; Parkinson's disease; Pathogenesis; Software; Statistical analysis
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.162763

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.