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Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model

Parkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (...

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Autores principales: Pradhan, Priyadarshika, Majhi, Olivia, Biswas, Abhijit, Joshi, Vinod Kumar, Sinha, Devanjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484898/
https://www.ncbi.nlm.nih.gov/pubmed/32913179
http://dx.doi.org/10.1038/s41419-020-02942-8
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author Pradhan, Priyadarshika
Majhi, Olivia
Biswas, Abhijit
Joshi, Vinod Kumar
Sinha, Devanjan
author_facet Pradhan, Priyadarshika
Majhi, Olivia
Biswas, Abhijit
Joshi, Vinod Kumar
Sinha, Devanjan
author_sort Pradhan, Priyadarshika
collection PubMed
description Parkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP(+). Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.
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spelling pubmed-74848982020-09-21 Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model Pradhan, Priyadarshika Majhi, Olivia Biswas, Abhijit Joshi, Vinod Kumar Sinha, Devanjan Cell Death Dis Article Parkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP(+). Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens. Nature Publishing Group UK 2020-09-10 /pmc/articles/PMC7484898/ /pubmed/32913179 http://dx.doi.org/10.1038/s41419-020-02942-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pradhan, Priyadarshika
Majhi, Olivia
Biswas, Abhijit
Joshi, Vinod Kumar
Sinha, Devanjan
Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title_full Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title_fullStr Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title_full_unstemmed Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title_short Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
title_sort enhanced accumulation of reduced glutathione by scopoletin improves survivability of dopaminergic neurons in parkinson’s model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484898/
https://www.ncbi.nlm.nih.gov/pubmed/32913179
http://dx.doi.org/10.1038/s41419-020-02942-8
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