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Dopamine Oxidation and Autophagy

The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the ne...

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Autores principales: Muñoz, Patricia, Huenchuguala, Sandro, Paris, Irmgard, Segura-Aguilar, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433151/
https://www.ncbi.nlm.nih.gov/pubmed/22966478
http://dx.doi.org/10.1155/2012/920953
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author Muñoz, Patricia
Huenchuguala, Sandro
Paris, Irmgard
Segura-Aguilar, Juan
author_facet Muñoz, Patricia
Huenchuguala, Sandro
Paris, Irmgard
Segura-Aguilar, Juan
author_sort Muñoz, Patricia
collection PubMed
description The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxic α-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i) the formation of α-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii) the formation of adducts with α- and β-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.
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spelling pubmed-34331512012-09-10 Dopamine Oxidation and Autophagy Muñoz, Patricia Huenchuguala, Sandro Paris, Irmgard Segura-Aguilar, Juan Parkinsons Dis Review Article The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxic α-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i) the formation of α-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii) the formation of adducts with α- and β-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes. Hindawi Publishing Corporation 2012 2012-08-26 /pmc/articles/PMC3433151/ /pubmed/22966478 http://dx.doi.org/10.1155/2012/920953 Text en Copyright © 2012 Patricia Muñoz et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Muñoz, Patricia
Huenchuguala, Sandro
Paris, Irmgard
Segura-Aguilar, Juan
Dopamine Oxidation and Autophagy
title Dopamine Oxidation and Autophagy
title_full Dopamine Oxidation and Autophagy
title_fullStr Dopamine Oxidation and Autophagy
title_full_unstemmed Dopamine Oxidation and Autophagy
title_short Dopamine Oxidation and Autophagy
title_sort dopamine oxidation and autophagy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433151/
https://www.ncbi.nlm.nih.gov/pubmed/22966478
http://dx.doi.org/10.1155/2012/920953
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