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Tytuł oryginału: Oxidation of dopamine to aminochrome as a mechanism for neurodegeneration of dopaminergic systems in Parkinson's disease. Possible neuroprotective role of DT-diaphorase.
Autorzy: Graumann Rebecca, Paris Irmgard, Martinez-Alvorado Pedro, Rumanwue Pamela, Perez-Pastene Carolina, Cardenas Sergio P., Marin Pablo, Diaz-Grez Fernando, Caviedes Raul, Caviedes Pablo, Segura-Aguilar Juan
Źródło: Pol. J. Pharmacol. 2002: 54 (6) s.573-579, il., bibliogr. 32 poz.
Sygnatura GBL: 313,156

Hasła klasyfikacyjne GBL:
  • neurologia

    Typ dokumentu:
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • ludzie
  • zwierzęta
  • szczury

    Streszczenie angielskie: Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson's disease, the exact mechanims of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which oxidizes to aminochrome as a consequence of: (i) overproduction of dopamine, (ii) inhibition and/or low expression of synaptic vesicle catecholamine transporter, (iii) inhibition or low expression of monoamine oxidases; (b) one-electron reduction of aminochrome to leukoaminochrome o-semiquinone radical, which induces neurotoxicity, due to inhibition of DT-diaphorase or the existence of a polymorphism wiht a point mutation (C- T) in the cDNA 609 expressing an inactive DT-diaphorase. We suggest that DT-diaphorase plays an neuroprotective role in dopaminergic neurons, which is supported by the following observations: (i) Cu-toxicity is dependent on DT-diaphorase inhibition with diocoumarol in RCSN-3 cells derived from the substantia nigra, (ii) the cytotoxic effect of monoamine oxidase-A inhbitor amiflamine in RCSN-3 cells is increased by 2.4-fold (p 0.001) in the presence of the inhibitor of DT-diaphorase, dicoumarol, (iii) concomitant intracerebral administration of manganese (Mn3+) together with the DT-diaphorase inhibitor dicoumarol into the left medial forebrain bundle produced a behavioral pattern characterized by contralateral rotational behavior when the rats were stimulated...

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