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Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

Parkinson’s disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated in the pathogenesis of PD. Genetic and environmental...

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Autores principales: Wang, Yumin, Gao, Luyan, Chen, Jichao, Li, Qiang, Huo, Liang, Wang, Yanchao, Wang, Hongquan, Du, Jichen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650509/
https://www.ncbi.nlm.nih.gov/pubmed/34887759
http://dx.doi.org/10.3389/fphar.2021.757161
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author Wang, Yumin
Gao, Luyan
Chen, Jichao
Li, Qiang
Huo, Liang
Wang, Yanchao
Wang, Hongquan
Du, Jichen
author_facet Wang, Yumin
Gao, Luyan
Chen, Jichao
Li, Qiang
Huo, Liang
Wang, Yanchao
Wang, Hongquan
Du, Jichen
author_sort Wang, Yumin
collection PubMed
description Parkinson’s disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated in the pathogenesis of PD. Genetic and environmental factors can produce OS, which has been implicated as a core contributor to the initiation and progression of PD through the degeneration of dopaminergic neurons. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) orchestrates activation of multiple protective genes, including heme oxygenase-1 (HO-1), which protects cells from OS. Nrf2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. Recently, a series of studies have reported that different bioactive compounds were shown to be able to activate Nrf2/antioxidant response element (ARE) and can ameliorate PD-associated neurotoxin, both in animal models and in tissue culture. In this review, we briefly overview the sources of OS and the association between OS and the pathogenesis of PD. Then, we provided a concise overview of Nrf2/ARE pathway and delineated the role played by activation of Nrf2/HO-1 in PD. At last, we expand our discussion to the neuroprotective effects of pharmacological modulation of Nrf2/HO-1 by bioactive compounds and the potential application of Nrf2 activators for the treatment of PD. This review suggests that pharmacological modulation of Nrf2/HO-1 signaling pathway by bioactive compounds is a therapeutic target of PD.
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spelling pubmed-86505092021-12-08 Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease Wang, Yumin Gao, Luyan Chen, Jichao Li, Qiang Huo, Liang Wang, Yanchao Wang, Hongquan Du, Jichen Front Pharmacol Pharmacology Parkinson’s disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated in the pathogenesis of PD. Genetic and environmental factors can produce OS, which has been implicated as a core contributor to the initiation and progression of PD through the degeneration of dopaminergic neurons. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) orchestrates activation of multiple protective genes, including heme oxygenase-1 (HO-1), which protects cells from OS. Nrf2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. Recently, a series of studies have reported that different bioactive compounds were shown to be able to activate Nrf2/antioxidant response element (ARE) and can ameliorate PD-associated neurotoxin, both in animal models and in tissue culture. In this review, we briefly overview the sources of OS and the association between OS and the pathogenesis of PD. Then, we provided a concise overview of Nrf2/ARE pathway and delineated the role played by activation of Nrf2/HO-1 in PD. At last, we expand our discussion to the neuroprotective effects of pharmacological modulation of Nrf2/HO-1 by bioactive compounds and the potential application of Nrf2 activators for the treatment of PD. This review suggests that pharmacological modulation of Nrf2/HO-1 signaling pathway by bioactive compounds is a therapeutic target of PD. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8650509/ /pubmed/34887759 http://dx.doi.org/10.3389/fphar.2021.757161 Text en Copyright © 2021 Wang, Gao, Chen, Li, Huo, Wang, Wang and Du. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Yumin
Gao, Luyan
Chen, Jichao
Li, Qiang
Huo, Liang
Wang, Yanchao
Wang, Hongquan
Du, Jichen
Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title_full Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title_fullStr Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title_full_unstemmed Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title_short Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease
title_sort pharmacological modulation of nrf2/ho-1 signaling pathway as a therapeutic target of parkinson’s disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650509/
https://www.ncbi.nlm.nih.gov/pubmed/34887759
http://dx.doi.org/10.3389/fphar.2021.757161
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