Neurotoxic mechanism of 1-methyl-4-phenyl-1,2,3,6-tetradropyridine

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BACKGROUND: To summarize the metabolic pathway of 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP)and its mechanism in inducing Parkinson disease.DATA SOURCES: A computer-based online search of Medline database was undertaken to identify articles about the metabolic pathway of MPTP and its mechanism in inducing Parkinson disease published in English between January 1996 and August 2004, the keywords were MPTP, Parkinson disease. Meanwhile, Chinese relevant articles published between January 2000 and August 2004 were searched in Wanfang database with the keywords of MPTP, Parkinson disease.STUDY SELECTION: More than 300 relevant literatures were retrieved, and the full-texts were further searched, those about the establishment of animal models, molecular mechanism of MPTP neurotoxicity and the metabolism were selected, and the obviously repetitive ones, case report and reviews were excluded, finally 18 of them were selected for summarization.DATA EXTRACTION: The 18 literatures were categorized according to MPTP induced animal models of Parkinson disease, mechanism of MPTP in inducing apoptosis in models of Parkinson disease, role of dopamine in the neurotoxic mechanism of MPTP, the role of reactive oxygen species and nitric oxide in the neurotoxicity of MPTP.DATA SYNTHESTS: Animal models of Parkinson disease induced by MPTP can not only produce the clinical characters of Parkinson disease, also duplicate the main biochemical and pathological changes of Parkinson disease. The metabolic pathway of MPTP and its mechanism in inducing Parkinson disease included producing free oxygen and nitric oxide, damaging mitochondrial respiratory chain, and inducing apoptosis, etc. Which could all lead to the degeneration and loss of dopaminergic neurons.CONCLUSTON: Although some aspects of the models of Parkinson disease are different from that in human beings, we can still know the neurodegeneration of Parkinson disease through studying the molecular mechanism of MPTP.
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