title: [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].
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.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Fudan University, Shanghai 200032, China. E-mail: cqzhu@shmu.edu.cn.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhao
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Shan
authors.forename: Cui-Qing
authors.initials: CQ
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000503:physiopathology*; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D025842:SUMO-1 Protein; D016875:tau Proteins