Neurotoxicity of MPTP.
After the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we acquired a good animal model of Parkinson's disease. The extraordinary recent growth in knowledge using MPTP parkinsonism has fostered increased understanding of Parkinson's disease. In the present paper, the discovery of MPTP and the biochemical, pathological, and clinical findings of MPTP parkinsonism are first reviewed briefly. Next, using MPTP parkinsonism, unresolved issuses such as the apoptosis of MPTP, levodopa toxicity, and neuroprotective effects of monoamine oxidase inhibitors or dopamine agonists are discussed. Finally, environmental factors such as the etiology of Parkinson's disease are examined. Some genetic factors that lead to familial Parkinson's disease have recently been reported, but most cases of Parkinson's disease are sporadic. Recent epidemiological evidence emphasizes an etiological relation of 18th and 19th century industrialization to Parkinson's disease. Man-made toxins, such as industrial chemicals and herbicides/pesticides, have been suggested to increase the risk of developing Parkinson's disease. I would like to highlight the significance of re-examination of environmental factors in the etiology of Parkinson's disease.
Fukuda
T
T
Department of Neuroscience, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan. fukuda@-t@jikei.ac.jp
D000818:Animals; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D020267:MPTP Poisoning / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology
D015259:Dopamine Agents; D004785:Environmental Pollutants; D007306:Insecticides; D018696:Neuroprotective Agents