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The DOI matches its Crossref record; 174 of the 174 references it cites were found in a registry or an index.

Protective and toxic roles of dopamine in Parkinson's disease

Open access
Segura‐Aguilar, Juan, Paris, Irmgard, Muñoz, Patricia, Ferrari, Emanuele, Zecca, Luigi, Zucca, Fabio A.·2014·Journal of Neurochemistry

Abstract

The molecular mechanisms causing the loss of dopaminergic neurons containing neuromelanin in the substantia nigra and responsible for motor symptoms of Parkinson's disease are still unknown. The discovery of genes associated with Parkinson's disease (such as alpha synuclein (SNCA), E3 ubiquitin protein ligase (parkin), DJ‐1 (PARK7), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL‐1), serine/threonine‐protein kinase (PINK‐1), leucine‐rich repeat kinase 2 (LRRK2), cation‐transporting ATPase 13A1 (ATP13A), etc.) contributed enormously to basic research towards understanding the role of these proteins in the sporadic form of the disease. However, it is generally accepted by the scientific community that mitochondria dysfunction, alpha synuclein aggregation, dysfunction of protein degradation, oxidative stress and neuroinflammation are involved in neurodegeneration. Dopamine oxidation seems to be a complex pathway in which dopamine o‐quinone, aminochrome and 5,6‐indolequinone are formed. However, both dopamine o‐quinone and 5,6‐indolequinone are so unstable that is difficult to study and separate their roles in the degenerative process occurring in Parkinson's disease. Dopamine oxidation to dopamine o‐quinone, aminochrome and 5,6‐indolequinone seems to play an important role in the neurodegenerative processes of Parkinson's disease as aminochrome induces: (i) mitochondria dysfunction, (ii) formation and stabilization of neurotoxic protofibrils of alpha synuclein, (iii) protein degradation dysfunction of both proteasomal and lysosomal systems and (iv) oxidative stress. The neurotoxic effects of aminochrome in dopaminergic neurons can be inhibited by: (i) preventing dopamine oxidation of the transporter that takes up dopamine into monoaminergic vesicles with low pH and dopamine oxidative deamination catalyzed by monoamino oxidase (ii) dopamine o‐quinone, aminochrome and 5,6‐indolequinone polymerization to neuromelanin and (iii) two‐electron reduction of aminochrome catalyzed by DT‐diaphorase. Furthermore, dopamine conversion to NM seems to have a dual role, protective and toxic, depending mostly on the cellular context.image Dopamine oxidation to dopamine o‐quinone, aminochrome and 5,6‐indolequinone plays an important role in neurodegeneration in Parkinson's disease since they induce mitochondria and protein degradation dysfunction; formation of neurotoxic alpha synuclein protofibrils and oxidative stress. However, the cells have a protective system against dopamine oxidation composed by dopamine uptake mediated by Vesicular monoaminergic transporter‐2 (VMAT‐2), neuromelanin formation, two‐electron reduction and GSH‐conjugation mediated by Glutathione S‐transferase M2‐2 (GSTM2).

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Metadata

Authors
Segura‐Aguilar, J., Paris, I., Muñoz, P., Ferrari, E., Zecca, L., & Zucca, F. A.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2014-03-18
Volume
129
Issue
6
Pages
898-915
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2000293969
Cited by
498
References
174
FWCI
18.63
Type
journal article
Language
en
Open access
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