Chuang C. Chiueh

Bio: Chuang C. Chiueh is an academic researcher from National Institutes of Health. The author has contributed to research in topics: MPTP & Dopamine. The author has an hindex of 43, co-authored 79 publications receiving 5864 citations. Previous affiliations of Chuang C. Chiueh include Taipei Medical University.

Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism.

Abstract: The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces an irreversible neurological syndrome in man and monkey which is similar to idiopathic Parkinson's disease in its clinical, pathological, neurochemical and pharmacological response properties. MPTP is selectively neurotoxic to the dopaminergic regions of the brain, destroying neurones in the substantia nigra (A8 and A9 cells, nigrostriatal system) but not the ventral tegmental area (A10 cells, mesolimbic system). Selective dopamine depletion and nigral cell loss after MPTP treatment has also been reported recently in the mouse. The mechanism by which a peripherally administered, low-molecular weight compound exerts permanent but selective toxic effects on dopamine systems in the brain may be relevant to parkinsonian syndromes induced by other toxins and to the disease process in idiopathic Parkinson's disease. We report here that MPTP is oxidized in the brain to a pyridinium species (a compound with potent herbicidal activity) and, in the monkey, is trapped intraneuronally. Furthermore, we demonstrate that this enzymatic oxidation is blocked in vivo in the mouse by a monoamine oxidase inhibitor, a condition which also blocks the neurotoxicity, indicating that the oxidative metabolism of MPTP is required for its neurotoxic effect.

The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.

Abstract: The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.