Affiliations: [a] Department of Neurology and Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China | [b] Department of Neurology, Beijing Hospital, the Ministry of Health, Beijing, China
Correspondence:
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Corresponding author: Lili Wang, MD, Department of Neurology, Beijing Hospital, The Ministry of Health, Beijing 100730, China. Tel.: +8610 65121772; Fax: +8610 65212012; E-mail: [email protected].
Note: [] Communicated by Xiongwei Zhu
Abstract: As a natural product, (-)-Epigallocatechin-3-gallate (EGCG), has demonstrated remarkable neuronal protection by depressing oxidative stress in Parkinson's disease (PD). However, the molecular mechanisms underlying EGCG neuronal protection have not been clarified. Using 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma SH-SY5Y cells as a PD cell model, we found that 6-OHDA can cause neuronal death by regulating the activity of STAT3. Pretreatment of SH-SY5Y cells with EGCG (0.1–10 μM) significantly attenuated the cell death induced by 6-OHDA. In addition, the STAT3 activity decline induced by 6-OHDA in SH-SY5Y cells can be completely prevented by the presence of 1 μM of EGCG, and neuronal cell proliferation can be stimulated by EGCG treatment. These results clearly demonstrate that the disruption of STAT3 signaling by 6-OHDA makes significant contribution to the neuronal death in PD, and the protection of EGCG on neurons against oxidative stress-induced cell death may result from the re-stimulation of STAT3 signaling pathway. Our study not only clarified the role of STAT3 signaling pathway in oxidative stress-induced neuronal cell death, but also identified its involvement in the protection mechanism of EGCG on neurons in PD. The data resulting from our study also suggest that STAT3 may serve as a potential therapeutic target for the drug development in PD.
Keywords: (-)-Epigallocatechin-3-gallate (EGCG), 6-Hydroxydopamine (6-OHDA), neuroprotection, Parkinson's disease, signal transducers and activators of transcription (STAT)
