Generation of Neurotoxins by New Reaction Pathways of Dopamine under Oxidative Stress Conditions: Contributing Etiopathological Factors in Parkinson’s Disease

  • Alessandro Pezzella
  • Giuseppe Prota


A marked alteration of cellular redox equilibria is commonly recognized as a critical condition associated to Parkinson’s disease and related neurodegenerative disorders (Jenner et al., 1992). Whatever the primary cause of injury resulting in the selective loss or dysfunction of nigrostriatal dopamine neurons, the persisting condition of oxidative stress has been suggested as a major pathogenic factor (Fahn and Cohen, 1992). According to this vision an intricate cascade of intra- and extraneuronal events involving, inter alia, an alteration of GSH and ascorbate levels (Perry et al., 1982), a marked increase in lipid peroxidation and malondialdehyde levels and, most important, an accelerated cytosolic dopamine deamination by MAO (monoamine oxidase) (Cohen, 1986), coupled with iron accumulation should result in the generation of highly cytotoxic hydroxyl radical and superoxide anion by Fenton and Haber-Weiss type reactions, capable of triggering lipid peroxidation leading to membrane damage and eventually to neuronal death (Adam et al., 1991) as well as to the formation of dopamine-derived cytotoxic species such as 6-hydroxydopamine.


Isoquinoline Alkaloid Label Incorporation Ascorbate Level Oxidant Stress Hypothesis Nigrostriatal Dopamine Neuron 
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© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Alessandro Pezzella
    • 1
  • Giuseppe Prota
    • 1
  1. 1.Department of Organic and Biological ChemistryUniversity of Naples Federico IINaplesItaly

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