Neurotoxicity Research

, Volume 12, Issue 2, pp 125–134 | Cite as

Aminochrome as a preclinical experimental model to study degeneration of dopaminergic neurons in Parkinson’s disease

  • Irmgard Paris
  • Sergio Cardenas
  • Jorge Lozano
  • Carolina Perez-Pastene
  • Rebecca Graumann
  • Alejandra Riveros
  • Pablo Caviedes
  • Juan Segura-Aguilar
Article

Abstract

Four decades after L-dopa introduction to PD therapy, the cause of Parkinson’s disease (PD) remains unknown despite the intensive research and the discovery of a number of gene mutations and delections in the pathogenesis of familial PD. Different model neurotoxins have been used as preclinical experimental models to study the neurodegenerative process in PD, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and rotenone. The lack of success in identifying the molecular mechanism for the degenerative process in PD opens the question whether the current preclinical experimental models are suitable to understand the degeneration of neuromelanin-containing dopaminergic neurons in PD. We propose aminochrome as a model neurotoxin to study the neurodegenerative processes occurring in neuromelanin-containing dopaminergic neurons in PD. Aminochrome is an endogenous compound formed during dopamine oxidation and it is the precursor of neuromelanin, a substance whose formation is a normal process in mesencephalic dopaminergic neurons. However, aminochrome itself can induce neurotoxicity under certain aberrant conditions such as (i) one-electron reduction of aminochrome catalyzed by flavoenzymes to leukoaminochrome-o-semiquinone radical, which is a highly reactive neurotoxin; or (ii) the formation of aminochrome adducts with alpha-synuclein, enhancing and stabilizing the formation of neurotoxic protofibrils. These two neurotoxic pathways of aminochrome are prevented by DT-diaphorase, an enzyme that effectively reduces aminochrome with two-electrons, preventing both aminochrome one-electron reduction or formation alpha-synuclein protofibrils. We propose to use aminochrome as a preclinical experimental model to study the neurodegenerative process of neuromelanin-containing dopaminergic neurons in PD.

Keywords

Parkinson’s disease Aminochrome MPTP 6-Hydroxydopamine Rotenone alpha-Synuclein VMAT-2, Reserpine Copper Iron Dopamine 

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Copyright information

© Springer 2007

Authors and Affiliations

  • Irmgard Paris
    • 1
  • Sergio Cardenas
    • 1
  • Jorge Lozano
    • 1
  • Carolina Perez-Pastene
    • 1
  • Rebecca Graumann
    • 1
  • Alejandra Riveros
    • 1
  • Pablo Caviedes
    • 1
  • Juan Segura-Aguilar
    • 1
  1. 1.Programme of Molecular and Clinical Pharmacology, ICBM, Medical FacultyUniversity of ChileSantiagoChile

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