Research Papers: Gerotarget (Focus on Aging):

Piperine induces autophagy by enhancing protein phosphotase 2A activity in a rotenone-induced Parkinson’s disease model

Jia Liu, Min Chen, Xue Wang, Yi Wang, Chunli Duan, Ge Gao, Lingling Lu, Xia Wu, Xiaomin Wang and Hui Yang _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:60823-60843. https://doi.org/10.18632/oncotarget.11661

Metrics: PDF 2531 views  |   HTML 4683 views  |   ?  


Jia Liu1, Min Chen1, Xue Wang1, Yi Wang2, Chunli Duan1, Ge Gao1, Lingling Lu1, Xia Wu3, Xiaomin Wang1 and Hui Yang1

1 Department of Neurobiology, Capital Medical University, Center for Parkinson’s Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China

2 Department of Clinical Laboratory, China Rehabilitation Research Center, School of Rehabilitation Medicine, Capital Medical University, Beijing, China

3 School of Traditional Chinese Medicine, Capital Medical University, Beijing, China

Correspondence to:

Hui Yang, email:

Keywords: piperine; Parkinson’s disease; autophagy; PP2A; treatment; Gerotarget

Received: April 16, 2016 Accepted: August 24, 2016 Published: August 27, 2016


Parkinson’s disease (PD) is the second most common neurodegenerative disorder, but there are few treatments currently available. The autophagy pathway plays an important role in the pathogenesis of PD; modulating this pathway is considered to be a promising treatment strategy. Piperine (PIP) is a Chinese medicine with anti-inflammatory and antioxidant effects. The present study investigated the neuroprotective effects of PIP on rotenone-induced neurotoxicity in SK-N-SH cells, primary rat cortical neurons, and in a mouse model. Mice were administered rotenone (10mg/kg) for 6 weeks; PIP (25mg/kg, 50mg/kg) was subsequently administered for 4 weeks. We found that PIP treatment attenuated rotenone-induced motor deficits, and rescued the loss of dopaminergic neurons in the substantia nigra. PIP increased cell viability and restored mitochondrial functioning in SK-N-SH cells and primary neurons. In addition, PIP induced autophagy by inhibiting mammalian target of rapamycin complex 1(mTORC1) via activation of protein phosphotase 2A (PP2A). However, inhibiting PP2A activity with okadaic acid reduced these protective effects, suggesting that PP2A is a target of PIP. These findings demonstrate that PIP exerts neuroprotective effects in PD models via induction of autophagy, and may be an effective agent for PD treatment.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 11661