Histochemical features of stress-induced aggregates in α-synuclein overexpressing cells

Michiko Matsuzaki, Takafumi Hasegawa, Atsushi Takeda, Akio Kikuchi, Katsutoshi Furukawa, Yoji Kato, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

α-Synuclein is a major component of intracytoplasmic inclusions including Lewy bodies (LB), Lewy neurites (LN) and glial cytoplasmic inclusions, and plays a key role in neurodegenerative processes in Parkinson's disease (PD) and other synucleinopathies. Although the molecular mechanisms of the disease process still remain to be elucidated, recent studies have suggested that an interaction between reactive oxygen species (ROS) and α-synuclein may be closely associated with the initiation and/or the progression of synucleinopathies. In this study, we established human dopaminergic SH-SY5Y cell lines overexpressing wild-type or mutant α-synuclein and exposed them to various ROS generators. After the exposure to ROS, α-synuclein aggregates were formed in the cytoplasm of these cells, and these were immunopositive for ubiquitin, nitrotyrosine and dityrosine, and positive for thioflavin S staining. Thus, the obtained cytoplasmic aggregates shared many features with inclusion bodies in synucleinopathies. The γ-tubulin and molecular chaperones coexisted as well, suggesting that the aggregate formation is associated with the intracellular transport along microtubules and may reflect protective responses against neuronal insults. This cellular model not only will be informative for our understanding of the pathophysiological process in synucleinopathies, but also can be applied to the screening of neuroprotective molecules with therapeutic potential.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalBrain research
Volume1004
Issue number1-2
DOIs
Publication statusPublished - 2004 Apr 9

Keywords

  • Degenerative disease: Parkinson's
  • Disorders of the nervous system
  • Histochemical feature
  • Overexpressing cell
  • α-Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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