Accelerated α-synuclein aggregation after differentiation of SH-SY5Y neuroblastoma cells

Takafumi Hasegawa, Michiko Matsuzaki, Atsushi Takeda, Akio Kikuchi, Hirotoshi Akita, George Perry, Mark A. Smith, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

α-Synuclein (α-syn) is a major component of inclusion bodies in Parkinson's disease (PD) and other synucleinopathies. To clarify the possible roles of α-syn in the molecular pathogenesis of neurodegenerative diseases, we have established a novel cellular model based on the differentiation of SH-SY5Y cells that overexpress α-syn. In the presence of ferrous iron, differentiation of the cells led to the formation of large perinuclear inclusion bodies, which developed from scattered small aggregates seen in undifferentiated cells. The iron-induced α-syn-positive inclusions co-localized largely with ubiquitin, and some of them were positive for nitrotyrosine, lipid, γ-tubulin and dynein. Notably, treatment with nocodazole, a microtubule depolymerizing agent, interrupted the aggregate formation but led to a concomitant increase of apoptotic cells. Therefore, it appears that an intracellular retrograde transport system via microtubules plays a crucial role in the aggregate formation and also that the aggregates may represent a cytoprotective response against noxious stimuli. This cellular model will enable better understanding of the molecular pathomechanisms of synucleinopathy.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalBrain research
Volume1013
Issue number1
DOIs
Publication statusPublished - 2004 Jul 2

Keywords

  • Aggregation
  • CAT
  • Degenerative disease: Parkinson's
  • Disorders of the nervous system
  • Iron
  • LBs
  • Lewy bodies
  • Lewy body
  • Neuroblastoma
  • PD
  • Parkinson's disease
  • WT
  • wild-type
  • α-Synuclein
  • α-syn
  • α-synuclein

ASJC Scopus subject areas

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

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