The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)

Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn<sup>3+</sup>) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, prote...

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Main Authors: Zhi Dong Zhou, Shao Ping Xie, Wuan Ting Saw, Patrick Ghim Hoe Ho, Hong Yan Wang, Lei Zhou, Yi Zhao, Eng King Tan
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/8/911
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spelling doaj-cf5f1a0a519c46a884f5665529f4eb612020-11-25T02:20:26ZengMDPI AGCells2073-44092019-08-018891110.3390/cells8080911cells8080911The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)Zhi Dong Zhou0Shao Ping Xie1Wuan Ting Saw2Patrick Ghim Hoe Ho3Hong Yan Wang4Lei Zhou5Yi Zhao6Eng King Tan7Department of Research, National Neuroscience Institute, Singapore 308433, SingaporeDepartment of Research, National Neuroscience Institute, Singapore 308433, SingaporeDepartment of Research, National Neuroscience Institute, Singapore 308433, SingaporeDepartment of Research, National Neuroscience Institute, Singapore 308433, SingaporeSignature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857, SingaporeOcular Proteomics Laboratory, Singapore Eye Research Institute, Singapore 169856, SingaporeDepartment of Neurology, Singapore General Hospital, Singapore 169608, SingaporeDepartment of Research, National Neuroscience Institute, Singapore 308433, SingaporeAccumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn<sup>3+</sup>) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, proteasome inhibition, and selective DA neuron vulnerability, which is implicated in the pathogenesis of Parkinson&#8217;s disease (PD). The DA oxidation can generate deleterious reactive oxygen species (ROS) and highly reactive DA quinones (DAQ) to induce DA-related toxicity, which can be alleviated by DA oxidation suppressors, ROS scavengers, DAQ quenchers, and MAOB inhibitors. On the other hand, the nuclear factor erythroid 2-related factor 2 (Nrf2)-Keap1 and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1&#945;) anti-oxidative and proliferative signaling pathways play roles in anti-oxidative cell defense and mitochondria biogenesis, which is implicated in DA neuron protections. Therefore, agents with capabilities to suppress DA-related toxicity including inhibition of DA oxidation, scavenge of ROS, detoxification of DAQ, inhibition of MAOB, and modulations of anti-oxidative signaling pathways can be protective to DA neurons. Accumulative evidence shows that tea or coffee consumptions and smoking are related to deceased PD prevalence with unknown mechanisms. In this study, we investigate the protective capabilities of tea polyphenols and other PD relevant agents to inhibit DA-related toxicity and protect against environmental or genetic factors induced DA neuron degeneration in vitro and in vivo. We find that tea polyphenols can significantly suppress DA-related toxicity to protect DA neurons. The tea polyphenols can protect DA neurons via inhibition of DA oxidation, conjugation with DAQ, scavenge of ROS, inhibition of MAOB, and modulations of Nrf2-Keap1 and PGC-1&#945; anti-oxidative signaling pathways. The tea polyphenols with more phenolic hydroxyl groups and ring structures have stronger protective functions. The protective capabilities of tea polyphenols is further strengthened by evidence that phenolic hydroxyl groups can directly conjugate with DAQ. However, GSH and other sulfhydyl groups containing agents have weaker capabilities to abrogate DA oxidation, detoxify ROS and DAQ and inhibit MAOB; whereas nicotine (NICO) and caffeine (CAF) can only modulate Nrf2-Keap1 and PGC-1&#945; pathways to protect DA neurons weakly. The tea polyphenols are identified to protect against overexpression of mutant A30P &#945;-synuclein (&#945;-syn) induced DA neuron degeneration and PD-like symptoms in transgenic Drosophila. Based on achievements from current studies, the excellent and versatile protective capabilities of tea polyphenols are highlighted, which will contribute and benefit to future anti-PD therapy.https://www.mdpi.com/2073-4409/8/8/911dopamineneurodegenerationpolyphenolsParkinson’s diseaseanti-PD therapy
collection DOAJ
language English
format Article
sources DOAJ
author Zhi Dong Zhou
Shao Ping Xie
Wuan Ting Saw
Patrick Ghim Hoe Ho
Hong Yan Wang
Lei Zhou
Yi Zhao
Eng King Tan
spellingShingle Zhi Dong Zhou
Shao Ping Xie
Wuan Ting Saw
Patrick Ghim Hoe Ho
Hong Yan Wang
Lei Zhou
Yi Zhao
Eng King Tan
The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
Cells
dopamine
neurodegeneration
polyphenols
Parkinson’s disease
anti-PD therapy
author_facet Zhi Dong Zhou
Shao Ping Xie
Wuan Ting Saw
Patrick Ghim Hoe Ho
Hong Yan Wang
Lei Zhou
Yi Zhao
Eng King Tan
author_sort Zhi Dong Zhou
title The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
title_short The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
title_full The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
title_fullStr The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
title_full_unstemmed The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)
title_sort therapeutic implications of tea polyphenols against dopamine (da) neuron degeneration in parkinson’s disease (pd)
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2019-08-01
description Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn<sup>3+</sup>) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, proteasome inhibition, and selective DA neuron vulnerability, which is implicated in the pathogenesis of Parkinson&#8217;s disease (PD). The DA oxidation can generate deleterious reactive oxygen species (ROS) and highly reactive DA quinones (DAQ) to induce DA-related toxicity, which can be alleviated by DA oxidation suppressors, ROS scavengers, DAQ quenchers, and MAOB inhibitors. On the other hand, the nuclear factor erythroid 2-related factor 2 (Nrf2)-Keap1 and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1&#945;) anti-oxidative and proliferative signaling pathways play roles in anti-oxidative cell defense and mitochondria biogenesis, which is implicated in DA neuron protections. Therefore, agents with capabilities to suppress DA-related toxicity including inhibition of DA oxidation, scavenge of ROS, detoxification of DAQ, inhibition of MAOB, and modulations of anti-oxidative signaling pathways can be protective to DA neurons. Accumulative evidence shows that tea or coffee consumptions and smoking are related to deceased PD prevalence with unknown mechanisms. In this study, we investigate the protective capabilities of tea polyphenols and other PD relevant agents to inhibit DA-related toxicity and protect against environmental or genetic factors induced DA neuron degeneration in vitro and in vivo. We find that tea polyphenols can significantly suppress DA-related toxicity to protect DA neurons. The tea polyphenols can protect DA neurons via inhibition of DA oxidation, conjugation with DAQ, scavenge of ROS, inhibition of MAOB, and modulations of Nrf2-Keap1 and PGC-1&#945; anti-oxidative signaling pathways. The tea polyphenols with more phenolic hydroxyl groups and ring structures have stronger protective functions. The protective capabilities of tea polyphenols is further strengthened by evidence that phenolic hydroxyl groups can directly conjugate with DAQ. However, GSH and other sulfhydyl groups containing agents have weaker capabilities to abrogate DA oxidation, detoxify ROS and DAQ and inhibit MAOB; whereas nicotine (NICO) and caffeine (CAF) can only modulate Nrf2-Keap1 and PGC-1&#945; pathways to protect DA neurons weakly. The tea polyphenols are identified to protect against overexpression of mutant A30P &#945;-synuclein (&#945;-syn) induced DA neuron degeneration and PD-like symptoms in transgenic Drosophila. Based on achievements from current studies, the excellent and versatile protective capabilities of tea polyphenols are highlighted, which will contribute and benefit to future anti-PD therapy.
topic dopamine
neurodegeneration
polyphenols
Parkinson’s disease
anti-PD therapy
url https://www.mdpi.com/2073-4409/8/8/911
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