SUMO-1 marks subdomains within glial cytoplasmic inclusions of multiple system atrophy

Neurosci Lett. 2005 Jun 10-17;381(1-2):74-9. doi: 10.1016/j.neulet.2005.02.013. Epub 2005 Mar 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cerebral Cortex / metabolism*
  • Cytoplasm / metabolism
  • Humans
  • Inclusion Bodies / metabolism*
  • Lewy Body Disease / metabolism*
  • Multiple System Atrophy / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Neuroglia / metabolism*
  • SUMO-1 Protein / metabolism*
  • Synucleins
  • Tissue Distribution
  • alpha-Synuclein


  • Biomarkers
  • Nerve Tissue Proteins
  • SNCA protein, human
  • SUMO-1 Protein
  • Synucleins
  • alpha-Synuclein