The possible role of one-electron reduction of aminochrome in the neurodegenerative process of the dopaminergic system
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- Segura-Aguilar, J., Metodiewa, D. & Baez, S. neurotox res (2001) 3: 157. doi:10.1007/BF03033188
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We present for discussion a possible molecular mechanism explaining the formation of reactive oxygen species involved in the neurodegenerative process of dopaminergic system in Parkinson’s disease. This new hypothesis involves one-electron reduction of aminochrome too-semiquinone radical, which seems to be the reaction responsible for neurodegenerative process of dopaminergic system. Leukoaminochromeo-semiquinone is extremely reactive with oxygen, which reoxidizes by reducing oxygen to superoxide radicals. Superoxide radicals enzymatically or spontaneously dismutate to dioxygen and hydrogen peroxide which is a precursor of hydroxyl radicals. ESR-experiments have showed that leukoaminochromeo-semiquinone is extremely reactive in the presence of oxygen compared to dopamineo-semiquinone. In addition, the antioxidant enzyme superoxide dismutase and catalase play a prooxidant role by increasing the autoxidation rate and formation of superoxide radicals. One electron reduction of aminochrome too-semiquinone can be performed by flavoenzymes, which use NADPH and NADH as electron donator. The ability of leukoaminochromeo-semiquinone to autoxidizes in the presence of oxygen give rise a redox cycling process which will continue until oxygen, NADH and / or NADPH are depleted. Depletion of NADPH will prevent glutathione reductase from reducing glutathione, which is one of the main antioxidants in the cell. In addition depletion of NADH will prevent the formation of ATP in the electron transport chain in the mitochondria. Two antioxidant, probably, neuroprotective reactions are also discussed.