TEA POLYPHENOLS ALLEVIATE MOTOR IMPAIRMENTS, DOPAMINERGIC NEURONAL INJURY, AND CEREBRAL α-SYNUCLEIN AGGREGATION IN MPTP-INTOXICATED PARKINSONIAN MONKEYS

Tea polyphenols (TPs) are bioactive flavanolrelated 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 alpha-synuclein (alpha-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 alpha-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 alpha-syn oligomers in neurons treated with alpha-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 alpha-syn aggregation in nonhuman primates. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.