title: SUMO-1 marks subdomains within glial cytoplasmic inclusions of multiple system atrophy.
abstract: Conjugation of the small ubiquitin-like modifier, SUMO-1, to target proteins is linked to the regulation of multiple cellular pathways, including nucleocytoplasmic trafficking, cell cycle progression, the ubiquitin-proteasome system and apoptosis. Recently, the accumulation of SUMOylated proteins in pathological neuronal intranuclear aggregates has been found in several neurodegenerative diseases. The aim of our study was to examine SUMO-1 in the alpha-synucleinopathy diseases, Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB). We conducted anti-SUMO-1 immunostaining of fixed brain tissue sections and smears of unfixed brain tissue homogenates of DLB and MSA cases. We found that oligodendroglial cytoplasmic inclusions, the alpha-synuclein-positive cytoplasmic aggregates that characterize MSA, exhibit robust punctate SUMO-1 immunostaining, marking discrete submicron-sized subdomains within the inclusion bodies. Lewy bodies in smears of DLB tissue homogenates showed similar SUMO-1-positive structures, although these were not detected in fixed tissue. In cell culture experiments, we found that the nuclear and perinuclear accumulation of SUMO-1 aggregates could be induced in glioma cells by chemical inhibition of proteasomal protein degradation.
authors.affiliation: Department of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, Australia. d.pountney@griffith.edu.au
authors.forename: D L
authors.initials: DL
authors.lastname: Pountney
authors.forename: F
authors.initials: F
authors.lastname: Chegini
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.forename: P C
authors.initials: PC
authors.lastname: Blumbergs
authors.forename: W P
authors.initials: WP
authors.lastname: Gai
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000378:metabolism*; D019578:Multiple System Atrophy / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D051843:Synucleins; D014018:Tissue Distribution; D051844:alpha-Synuclein
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D025842:SUMO-1 Protein; D051843:Synucleins; D051844:alpha-Synuclein