Theaflavins stimulate autophagic degradation of α-synuclein in neuronal cells

Given the recent epidemiological evidence showing an inverse correlation between black tea intake and the risk of Parkinson’s disease, it is an intriguing possibility that theaflavins, major natural polyphenols contained in black tea, may have an anti-neurodegenerative action. In this communication, we show that theaflavins act stimulatingly on autophagy in neuronal cells. Treatment of murine Neuro2A cells with theaflavin-3,3’-digallate (TF-3,3’) under the serum-free conditions resulted in stimulation of LC3-II expression and formation of LC3positive, double-membrane autophagosomes. Under the same conditions, lysosomal activity was little affected by TF-3,3’, while the upregulation of LC3-II by TF-3,3’ was abrogated by 3-methyadenine treatment. Further studies revealed that TF-3,3’ might stimulate degradation of Akt at proteasome, leading to suppression of mTOR phosphorylation and enhancement of autophagy. Finally, expression of the transfected α-synuclein in these cells was significantly decreased by treatment with TF-3,3’. These results suggest that theaflavins’ autophagystimulating action might account for the prophylactic effects of black tea on Parkinson’s disease.