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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01428

Autophagy activation is involved in acidic fibroblast growth factor ameliorating Parkinson's disease via regulating tribbles homologue 3

Xingfeng Zhong1, Beini Wang2, Guanyinsheng Zhang1, Yuan Yuan2, Xiaoli Hu1, Jun Xiong2, Peipei Zheng2, Yaqian Liu2,  Ke Xu3,  Jian Xiao2,  Yanqing Wu4 and Junming Ye1*
  • 1First Affiliated Hospital of Gannan Medical University, China
  • 2School of Pharmaceutical Sciences, Wenzhou Medical University, China
  • 3Wenzhou Medical University, China
  • 4Wenzhou University, China

Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, resulting in loss of dopamine neurons. Excessive endoplasmic reticulum (ER) stress and autophagy dysfunction play a crucial role on Parkinson's disease (PD) development. It has been showed that acidic fibroblast growth factor (aFGF) alleviates the development of PD by inhibiting ER stress. But the role of autophagy and its relationship with ER stress during aFGF treatment for PD has not been elucidated. We found that both aFGF and rapamycin (Rapa) improved 6-Hydroxy Dopamine (6-OHDA)-induced PD development as shown with histomorphology results in striatum and substantia nigra (SNpc). Additionally, aFGF promoted autophagy with increasing mTOR and decreasing p62 expressions, and then exerts its neuroprotective role in 6-OHDA-treated PC12 cells, which were abolished by chloroquine (CQ) treatment. Moreover, 4-phenylbutyric acid (4-PBA) administration inhibited the expressions of autophagy markers during 6-OHDA-treated PC12 cells, which was similar with aFGF treating PC12 cells under 6-OHDA condition. Furthermore, we had detected the expressions of CHOP and its downstream factor, tribbles homologue 3 (TRB3), a pro-apoptotic protein. We found that TRB3 and CHOP expressions were significantly downregulated after treating with aFGF and 4-PBA in 6-OHDA-treated PC12 cells and PD model. Taken together, this study has demonstrated that aFGF treatment ameliorates 6-OHDA-induced elevated ER stress and subsequently suppression of autophagy via inhibiting TRB3 activation, and consequently ameliorates 6-OHDA-induced neurotoxicity.

Keywords: Parkinson's disease, Acidic fibroblast growth factor (aFGF), Autophagy, Endoplasmic reticulum (ER) stress, tribbles homologue 3 (TRB3)

Received: 03 Sep 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Zhong, Wang, Zhang, Yuan, Hu, Xiong, Zheng, Liu, Xu, Xiao, Wu and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Junming Ye, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China, yjm7798@sina.com