The role of α-synuclein ubiquitination in its selectivity of degradation pathway
10.3969/j.issn.1006-5725.2015.11.009
- VernacularTitle:抑制SIAH-1功能对α-synuclein选择降解通路的影响
- Author:
Zenglin CAI
;
Yuanyuan LIU
;
Shouru XUE
;
Jing XU
;
Qingzhi ZHANG
;
Xiuming LI
- Publication Type:Journal Article
- Keywords:
Seven in absentia homolog;
MPP+;
α-synuclein;
Parkinson′s disease;
Autophagy;
Ubiquitin-proteasome system
- From:
The Journal of Practical Medicine
2015;(11):1758-1762
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate SIAH′s role in α-synuclein degradation, formation of Lewy bodies and neuronal death. Methods Proliferative activity of PC12 cells was measures by MTT assay after treatment with MPP and Rapamycin. Western Blot was applied determine the protein expression of LC3-Ⅱ, E1, SIAH-1, P53 and α-synucleinto. PCR was applied to measure protein related mRNA levels. Immunofluorescent techniques were used to detect the distribution of α-synuclein, SIAH-1 and LC3 in cells after SIAH antibody processing. Results MPP+ treatment increased α-synuclein, E1 expression and SIAH-1 activity, however, LC3-Ⅱ, P53 and α-synuclein protein levels decreased significantly. Anti-SIAH-1 antibody treatment reversed this trend, with E1 significantly increased. Rapamycin treatment reduced SIAH-1 and α-synuclein levels in the MPP+ group. SIAH-1 antibody significantly decreased the positive immuno-stain of α-synuclein, SIAH-1 and LC3, suggesting loss of co-localization. Conclusions Anti-SIAH-1 supports the clearance of non-aggregated α-synuclein by the UPS. SIAH plays a key role in the pathogenesis of Parkinson′s disease and is a potential therapeutic target of neurodegenerative diseases.
