Potential involvement of abnormal increased SUMO-1 in modulation of the formation of Alzheimer's disease senile plaques and neuritic dystrophy in APP/PS1 transgenic mice.
- Author:
Xiao-Yan ZHAO
1
;
Dan-Dan WANG
;
Ye SHAN
;
Cui-Qing ZHU
Author Information
1. State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China. E-mail: cqzhu@shmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Alzheimer Disease;
physiopathology;
Amyloid beta-Peptides;
metabolism;
Amyloid beta-Protein Precursor;
metabolism;
Animals;
Brain;
pathology;
Mice;
Mice, Transgenic;
Neurites;
pathology;
Phosphorylation;
Plaque, Amyloid;
physiopathology;
SUMO-1 Protein;
metabolism;
Sumoylation;
tau Proteins;
metabolism
- From:
Acta Physiologica Sinica
2013;65(3):253-262
- CountryChina
- Language:Chinese
-
Abstract:
Small ubiquitin-related modifiers (SUMOs) belong to an important class of ubiquitin like proteins. SUMOylation is a post-translational modification process that regulates the functional properties of many proteins, among which are several proteins implicated in neurodegenerative diseases. This study was aimed to investigate the changes of SUMO-1 expression and modification, and the relationship between SUMO-1 and Alzheimer's disease (AD) pathology in APP/PS1 transgenic AD mice. Using Western blot, co-immunoprecipitation and immunofluorescent staining methods, the SUMO-1 expression and modification and its relation to tau, amyloid precursor protein (APP) and β-amyloid protein (Aβ) in the 12-month-old APP/PS1 transgenic AD mice were analyzed. The results showed that: (1) Compared with the normal wild-type mice, the expression and modification of SUMO-1 increased in brain of AD mice, which was accompanied by an increase of ubiquitination; (2) In RIPA soluble protein fraction of cerebral cortex, co-immunoprecipitation analysis showed tau SUMOylated by SUMO-1 increased in AD mice, however, AT8 antibody labeled phosphorylated tau was less SUMOylated whereas PS422 antibody labeled phosphorylated tau was similar to control mice; (3) Double immunofluorescent staining showed that SUMO-1 could distributed in amyloid plaques, appearing that some of SUMO-1 diffused in centre of some plaques and some of SUMO-1 co-localized with AT8 labeled phosphorylated tau forming punctate aggregates around amyloid plaques which was concerned as dystrophic neurites, however, less Aβ, APP and PS422 labeled phosphorylated tau were found co-localized with SUMO-1. These results suggest that SUMO-1 expression and modification increase abnormally in transgenic AD mice, which may participate in modulation of the formation of senile plaques and dystrophic neurites.
