Oxidative stress: a role in the pathogenesis of Parkinson’s disease
The degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson’s disease (PD). However, the etiology of this degeneration is not known. Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease. An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper. The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN). Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD.
KeywordsTyrosine Hydroxylase Substantia Nigra Monoamine Oxidase Locus Coeruleus Lipoic Acid
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- Birkmayer W, Riederer P (1985) Die Parkinson-Krankheit, Biochemie, Klinik, Therapie. 2. Aufl. Springer, Wien New York.Google Scholar
- Cohen G (1983) The pathobiology of Parkinson’s disease: biochemical aspects of dopamine neuron senescence. J Neural Transm 19: 89–103.Google Scholar
- Hefti F, Melamed E, Bhawan J, Wurtman RJ (1981) Longterm administration of L-Dopa does not damage dopaminergic neurons in the mouse. Neurology 31: 1194–1195.Google Scholar
- Konradi C, Riederer P, Youdim MBH (1986) Hydrogen peroxide enhances the activity of monoamine type-B but not type A: a pilot study. J Neural Transm [Suppl 22]: 61-73.Google Scholar
- Konradi C, Kornhuber J, Frölich L, Fritze J, Heinsen H, Beckmann H, Schulz E, Riederer P (1989) Demonstration of MAO-A and-B in the human brain stem by a histochemical technique. Neuroscience (in press).Google Scholar
- Konradi C, Riederer P, Heinsen H (1989) Histochemistry of MAO subtypes in the brainstem of humans: a relation to the radical hypothesis of Parkinson’s disease. In: Przuntek H, Riederer P (eds) Early diagnosis and preventive therapy in Parkinson’s disease. Springer, Wien New York, pp 243–248.Google Scholar