title: Piperine induces autophagy by enhancing protein phosphotase 2A activity in a rotenone-induced Parkinson's disease model.
abstract: 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.
authors: 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.
authors: Jia
authors: J
authors: Liu
authors: 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.
authors: Min
authors: M
authors: Chen
authors: 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.
authors: Xue
authors: X
authors: Wang
authors: Department of Clinical Laboratory, China Rehabilitation Research Center, School of Rehabilitation Medicine, Capital Medical University, Beijing, China.
authors: Yi
authors: Y
authors: Wang
authors: 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.
authors: Chunli
authors: C
authors: Duan
authors: 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.
authors: Ge
authors: G
authors: Gao
authors: 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.
authors: Lingling
authors: L
authors: Lu
authors: School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
authors: Xia
authors: X
authors: Wu
authors: 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.
authors: Xiaomin
authors: X
authors: Wang
authors: 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.
authors: Hui
authors: H
authors: Yang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D002470:Cell Survival; D059290:Dopaminergic Neurons / Q000378:metabolism; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000201:enzymology*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051381:Rats; D012402:Rotenone; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052117:Benzodioxoles; D018696:Neuroprotective Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012402:Rotenone; D000076222:Mechanistic Target of Rapamycin Complex 1; C514014:Ppp2ca protein, rat; D054648:Protein Phosphatase 2; C008922:piperine
keywords: Gerotarget; PP2A; Parkinson’s disease; autophagy; piperine; treatment