Cellular pathophysiology of Parkinson's disease

Atsushi Takeda, Naoto Sugeno, Takafumi Hasegawa, Michiko Kobayashi, Akio Kikuchi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


To explore pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy, we developed cellular model for synucleinopathy. In this experimental model, α-synuclein was overexpressed in SH-SY5Y cells, which were then exposed to mitochondrial toxins. The data thus obtained suggested the followings. 1) By the treatment with rotenone, wild type α-synuclein overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies. 2) The aggregate formation of α-synuclein may be cytoprotective. 3) The catechol-derived quinones are candidate molecules to facilitate the oligomer formation of α-synuclein. 4) The cells overexpressing S129A mutant showed few aggregations. It is suggested that phosphorylation at serine 129 is essential for aggregate formation. 5) In wild-type α-synuclein cells treated with rotenone, unfolded protein response (UPR) markers were induced prior to the induction of mitochondrial disruption and caspase-3 activation. 6) On the other hand, the S129 A mutant failed to activate these UPRs. Thus it seems plausible that α-synuclein toxicity is dependent on the phosphorylation at S129.

Original languageEnglish
Pages (from-to)984-985
Number of pages2
JournalClinical Neurology
Issue number11
Publication statusPublished - 2008 Nov


  • Aggregation
  • ER stress
  • Quinines
  • Synucleinopathy


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