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 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.
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Zeng-Lin
0000-0002-7231-6050
ZL
Cai
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Jing
J
Xu
Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Shou-Ru
SR
Xue
Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Yuan-Yuan
YY
Liu
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Yong-Jin
YJ
Zhang
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Xin-Zhi
XZ
Zhang
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Xuan
X
Wang
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Fang-Ping
FP
Wu
Department of Neurology, Affiliated Lianyungang Hospital of Xuzhou Medical College, Lianyungang, Jiangsu Province, China.
Xiao-Min
XM
Li
1-methyl-4-phenylpyridinium; E3 ubiquitin ligase seven in absentia homolog 1; Parkinson's disease; autophagy; nerve regeneration; neural regeneration; neurodegeneration; rapamycin; ubiquitin-proteasome system