{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:02:27Z","timestamp":1790650947125,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore National Medical Research Council","award":["STaR and the clinical translational research programme in Parkinson\u2019s disease"],"award-info":[{"award-number":["STaR and the clinical translational research programme in Parkinson\u2019s disease"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn3+) 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\u2019s 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\u03b1) 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\u03b1 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\u03b1 pathways to protect DA neurons weakly. The tea polyphenols are identified to protect against overexpression of mutant A30P \u03b1-synuclein (\u03b1-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.<\/jats:p>","DOI":"10.3390\/cells8080911","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson\u2019s Disease (PD)"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0251-4163","authenticated-orcid":false,"given":"Zhi Dong","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Research, National Neuroscience Institute, Singapore 308433, Singapore"},{"name":"Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao Ping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Research, National Neuroscience Institute, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuan Ting","family":"Saw","sequence":"additional","affiliation":[{"name":"Department of Research, National Neuroscience Institute, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Ghim Hoe","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Research, National Neuroscience Institute, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ocular Proteomics Laboratory, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Research Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng King","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Research, National Neuroscience Institute, Singapore 308433, Singapore"},{"name":"Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Department of Neurology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/ageing\/23.4.342","article-title":"Review: The pathophysiology of the motor signs in Parkinson\u2019s disease","volume":"23","author":"Meara","year":"1994","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1176\/jnp.14.2.223","article-title":"An essay on the shaking palsy","volume":"14","author":"Parkinson","year":"2002","journal-title":"J. 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