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Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?

Parkinson’s disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest t...

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Detalles Bibliográficos
Autores principales: Mehta, Nihar J., Marwah, Praneet Kaur, Njus, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356376/
https://www.ncbi.nlm.nih.gov/pubmed/30654525
http://dx.doi.org/10.3390/cells8010059
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author Mehta, Nihar J.
Marwah, Praneet Kaur
Njus, David
author_facet Mehta, Nihar J.
Marwah, Praneet Kaur
Njus, David
author_sort Mehta, Nihar J.
collection PubMed
description Parkinson’s disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest that inadequate clearance may couple the two phenomena. If a neuron’s autophagy machinery is overwhelmed, whether by excessive oxidative stress or by excessive protein aggregation, protein aggregates and dysfunctional mitochondria will both accumulate. Parkinson’s disease may provide a unique window into this because there is evidence that both sides contribute. Mutations amplifying the aggregation of α-synuclein are associated with Parkinson’s disease. Likewise, mutations in Parkin and PINK1, proteins involved in mitophagy, suggest that impaired mitochondrial clearance is also a contributing factor. Many have suggested that dopamine oxidation products lead to oxidative stress accounting for the dopaminergic selectivity of the disease. We have presented evidence for the specific involvement of hypochlorite-oxidized cysteinyl-dopamine (HOCD), a redox-cycling benzothiazine derivative. While toxins like 6-hydroxydopamine and 1-methyl-4-phenyl pyridinium (MPP+) have been used to study mitochondrial involvement in Parkinson’s disease, HOCD may provide a more physiologically relevant approach. Understanding the role of mitochondrial dysfunction and oxidative stress in Parkinson’s disease and their relation to α-synuclein proteinopathy is important to gain a full picture of the cause, especially for the great majority of cases which are idiopathic.
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spelling pubmed-63563762019-02-06 Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin? Mehta, Nihar J. Marwah, Praneet Kaur Njus, David Cells Review Parkinson’s disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest that inadequate clearance may couple the two phenomena. If a neuron’s autophagy machinery is overwhelmed, whether by excessive oxidative stress or by excessive protein aggregation, protein aggregates and dysfunctional mitochondria will both accumulate. Parkinson’s disease may provide a unique window into this because there is evidence that both sides contribute. Mutations amplifying the aggregation of α-synuclein are associated with Parkinson’s disease. Likewise, mutations in Parkin and PINK1, proteins involved in mitophagy, suggest that impaired mitochondrial clearance is also a contributing factor. Many have suggested that dopamine oxidation products lead to oxidative stress accounting for the dopaminergic selectivity of the disease. We have presented evidence for the specific involvement of hypochlorite-oxidized cysteinyl-dopamine (HOCD), a redox-cycling benzothiazine derivative. While toxins like 6-hydroxydopamine and 1-methyl-4-phenyl pyridinium (MPP+) have been used to study mitochondrial involvement in Parkinson’s disease, HOCD may provide a more physiologically relevant approach. Understanding the role of mitochondrial dysfunction and oxidative stress in Parkinson’s disease and their relation to α-synuclein proteinopathy is important to gain a full picture of the cause, especially for the great majority of cases which are idiopathic. MDPI 2019-01-16 /pmc/articles/PMC6356376/ /pubmed/30654525 http://dx.doi.org/10.3390/cells8010059 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mehta, Nihar J.
Marwah, Praneet Kaur
Njus, David
Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title_full Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title_fullStr Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title_full_unstemmed Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title_short Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
title_sort are proteinopathy and oxidative stress two sides of the same coin?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356376/
https://www.ncbi.nlm.nih.gov/pubmed/30654525
http://dx.doi.org/10.3390/cells8010059
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