Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism.
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.
Asanuma
Masato
M
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan. asachan@cc.okayama-u.ac.jp
Miyazaki
Ikuko
I
Diaz-Corrales
Francisco J
FJ
Ogawa
Norio
N
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology*; D020734:Parkinsonian Disorders / Q000209:etiology*
D016227:Benzoquinones; D009498:Neurotoxins; C004532:quinone; D004298:Dopamine