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

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...

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Bibliographic Details
Main Authors: Zeng-lin Cai, Jing Xu, Shou-ru Xue, Yuan-yuan Liu, Yong-jin Zhang, Xin-zhi Zhang, Xuan Wang, Fang-ping Wu, Xiao-min Li
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2015-01-01
Series:Neural Regeneration Research
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Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2015;volume=10;issue=8;spage=1286;epage=1291;aulast=Cai
Description
Summary: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.
ISSN:1673-5374