Presence of N-Methylated β-Carbolinium Ions and Potential Neurotoxic Analogs of MPP+ in the Brain and Cerebrospinal Fluid of Parkinsonian and Non-Parkinsonian Patients
The etiology of Parkinson’s disease is unknown. N-Methyl-4-phenyl-tetrahydropyridine (MPTP), a contaminant originally found in synthetic “street heroin”, induces Parkinsonian like symptoms which arise from destruction of nigrostriatal neurons.1 After crossing the blood-brain-barrier, MPTP is oxidized intracerebrally in glia or non-dopaminergic neurons by monoamineoxidase B to an intermediate, N-methyl-4-phenyl-dihydropyridium ion, which disproportionates or is spontaneously oxidized to N-methyl-4-phenyl-tetrahydropyridinium ion (MPP+).2–4 The “MPTP story” led to considerations that environmental and/or endogenously generated substances with similar structures to MPTP may undergo brain bioactivation to mitochondrial toxicants. Recent studies have concentrated on iso-quinolines5–9 and β-carbolines (BCs).
KeywordsSubstantia Nigra Parkinsonian Patient Methylation Activity Dopamine Uptake Nigrostriatal Neuron
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