Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation

Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Ko Miyoshi, Norio Ogawa, Miho Murata

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The neurotoxicity of dopamine (DA) quinones as dopaminergic neuron-specific oxidative stress is considered to play a role in the pathogenesis and/or progression of Parkinson's disease (PD), since DA quinones conjugate with several key PD pathogenic molecules (e.g., tyrosine hydroxylase, α-synuclein and parkin) to form protein-bound quinone (quinoprotein) and consequently inhibit their functions. Zonisamide (ZNS) is used as an anti-epileptic agent but also improved the cardinal symptoms of PD in recent clinical trials in Japan. To evaluate the effects of ZNS on excess cytosolic free DA-induced quinone toxicity, we examined changes in DA quinone-related indices after ZNS treatment both in in vitro cell-free system and in cultured cells. Co-incubation of DA and ZNS in a cell-free system caused conversion of DA to stable melanin via formation of DA-semiquinone radicals and DA chrome. Long-term (5 days) treatment with ZNS decreased quinoprotein and increased DA/DOPA chromes in dopaminergic CATH.a cells. ZNS significantly inhibited quinoprotein formation induced by treatment with tetrahydrobiopterin and ketanserin that elevate cytosolic free DA in the cells. Our results suggest that the novel anti-parkinsonian agent ZNS possesses preventing effects against DA quinone formation induced by excess amount of cytosolic DA outside the synaptic vesicles.

Original languageEnglish
Pages (from-to)106-113
Number of pages8
JournalNeuroscience Research
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 2008

Fingerprint

zonisamide
Dopamine
Parkinson Disease
Cell-Free System
Synucleins
Ketanserin
Synaptic Vesicles
Dopaminergic Neurons
Melanins
Tyrosine 3-Monooxygenase
dopamine quinone

Keywords

  • Dopamine chrome
  • Dopamine quinone
  • Parkinson's disease
  • Quinoprotein
  • Zonisamide

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation. / Asanuma, Masato; Miyazaki, Ikuko; Diaz-Corrales, Francisco J.; Miyoshi, Ko; Ogawa, Norio; Murata, Miho.

In: Neuroscience Research, Vol. 60, No. 1, 01.2008, p. 106-113.

Research output: Contribution to journalArticle

Asanuma, Masato ; Miyazaki, Ikuko ; Diaz-Corrales, Francisco J. ; Miyoshi, Ko ; Ogawa, Norio ; Murata, Miho. / Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation. In: Neuroscience Research. 2008 ; Vol. 60, No. 1. pp. 106-113.
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