Acta Medica Okayama JUNE2008. Dopaminergic neuron-specific oxidative stress caused by dopamine itself. Ikuko Miyazaki Masato Asanuma

Transcription

1 Acta Medica Okayama Volume 62, Issue Article 1 JUNE2008 Dopaminergic neuron-specific oxidative stress caused by dopamine itself Ikuko Miyazaki Masato Asanuma Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, miyazaki@cc.okayama-u.ac.jp Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Copyright c 1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.

2 Dopaminergic neuron-specific oxidative stress caused by dopamine itself Ikuko Miyazaki and Masato Asanuma Abstract Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons. KEYWORDS: dopamine quinone, quinoprotein, methamphetamine, Parkinson?s disease, L-DOPA Copyright c 1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved PMID:

3 Miyazaki and Asanuma: Dopaminergic neuron-specific oxidative stress caused by dopamine Dopaminergic Neuron-Specific Oxidative Stress Caused by Dopamine Itself * ʼ ʼ Produced by The Berkeley Electronic Press,

4 Acta Medica Okayama, Vol. 62 [2008], Iss. 3, Art. 1 ʼ ʼ 2

5 Miyazaki and Asanuma: Dopaminergic neuron-specific oxidative stress caused by dopamine ʼ ʼ ʼ,,,,, Produced by The Berkeley Electronic Press,

6 Acta Medica Okayama, Vol. 62 [2008], Iss. 3, Art. 1 ʼ 4

7 Miyazaki and Asanuma: Dopaminergic neuron-specific oxidative stress caused by dopamine ʼ ʼ ʼ ʼ ʼ Produced by The Berkeley Electronic Press,

8 Acta Medica Okayama, Vol. 62 [2008], Iss. 3, Art. 1 ʼ 6

9 Miyazaki and Asanuma: Dopaminergic neuron-specific oxidative stress caused by dopamine ʼ ʼ ʼ Produced by The Berkeley Electronic Press,

10 Acta Medica Okayama, Vol. 62 [2008], Iss. 3, Art ʼ ʼ ʼ ʼ ʼ ʻ ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ

11 Miyazaki and Asanuma: Dopaminergic neuron-specific oxidative stress caused by dopamine ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ Produced by The Berkeley Electronic Press,

12 Acta Medica Okayama, Vol. 62 [2008], Iss. 3, Art ʼ