title: Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral α-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys.
abstract: Tea polyphenols (TPs) are bioactive flavanol-related catechins that have been shown to protect dopaminergic (DAergic) neurons against neurotoxin-induced injury in mouse Parkinson's disease (PD) models. However, the neuroprotective efficacy of TP has not been investigated in nonhuman PD primates, which can more accurately model the neuropathology and motor impairments of human PD patients. Here, we show that oral administration of TP alleviates motor impairments and DAergic neuronal injury in the substantia nigra in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated PD monkeys, indicating an association between protection against motor deficits and preservation of DAergic neurons. We also show a significant inhibition of MPTP-induced accumulation of neurotoxic α-synuclein (α-syn) oligomers in the striatum and other brain regions, which may contribute to the neuroprotection and improved motor function conferred by TP. The association between reduced α-syn oligomerization and neuroprotection was confirmed in cultured DAergic cells. The most abundant and bioactive TP in the mixture used in vivo, (-)-epigallocatechin-3-gallate, reduced intracellular levels of α-syn oligomers in neurons treated with α-syn oligomers, 1-methyl-4-phenylpyridiniumion, or both, accompanied by increased cell viability. The present study provides the first evidence that TP can alleviate motor impairments, DAergic neuronal injury, and α-syn aggregation in nonhuman primates.
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Human Anatomy, School of Basic Medical Sciences, Guilin Medical University, Guilin, China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China; Beijing Institute for Brain Disorders Parkinson's Disease Center, Beijing, China.
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China; Beijing Institute for Brain Disorders Parkinson's Disease Center, Beijing, China. Electronic address: yushun103@163.com.
authors.forename: S
authors.initials: S
authors.lastname: Yu
mesh_terms: D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005260:Female; D008252:Macaca fascicularis; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D051844:alpha-Synuclein; D002392:Catechin; C045651:epigallocatechin gallate; D004298:Dopamine
keywords: Parkinson’s disease; dopaminergic neuronal injury; motor impairments; tea polyphenols; α-synuclein aggregation