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Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model.
Biochem Pharmacol. 2017 09 15; 140:115-123.BP

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder with an incidence second only to Alzheimer's disease. The main pathological feature of PD is the death of dopaminergic neurons in the substantia nigra pars compacta. Nicotinic receptor agonists are neuroprotective in several PD models and there is considerable evidence that α7 nicotinic acetylcholine receptors (α7-nAChRs) are important therapeutic targets for neurodegenerative diseases. However, the involvement of α7-nAChRs and underlying signaling mechanisms in PD pathogenesis are unclear. The objective of the present study was to explore the potential functions of α7-nAChRs in PD pathology, and to determine whether these effects are exerted via Wnt/β-catenin signaling in a mouse PD model. In the in vivo study, α7-nAChR knockout (α7-KO) reversed the beneficial effects of nicotine on motor deficits, dopaminergic neuron loss, astrocyte and microglia activation, and reduced striatal dopamine release induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Injury to SH-SY5Y cells by 1-methyl-4-phenylpyridinium treatment was also ameliorated by nicotine, and this effect was abolished by methyllycaconitine (MLA), a selective α7-nAChR antagonist, or by siRNA-mediated α7-nAChR knockdown. Furthermore, nicotine increased expression levels of Wnt/β-catenin signaling proteins in the PD mouse model or in the SH-SY5Y cells treated by 1-methyl-4-phenylpyridinium, and these effects were also reversed by MLA or α7-siRNA treatment in vivo or in vitro. These results suggest that endogenous α7-nAChR mechanisms play a crucial role in a mouse PD model via regulation of Wnt/β-catenin signaling.

Authors+Show Affiliations

Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: yasmin@vip.sina.com.School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: lolhaoshuai@163.com.Department of Pharmacology, Nanjing Medical University, Nanjing 211166, China. Electronic address: infection118@163.com.Department of Pharmacology, Nanjing Medical University, Nanjing 211166, China. Electronic address: orthoexp89@gmail.com.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: orthosci@163.com.School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: ychen@njmu.edu.cn.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: junhu@njmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28551099

Citation

Liu, Yuan, et al. "Wnt/β-catenin Signaling Plays an Essential Role in Α7 Nicotinic Receptor-mediated Neuroprotection of Dopaminergic Neurons in a Mouse Parkinson's Disease Model." Biochemical Pharmacology, vol. 140, 2017, pp. 115-123.
Liu Y, Hao S, Yang B, et al. Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model. Biochem Pharmacol. 2017;140:115-123.
Liu, Y., Hao, S., Yang, B., Fan, Y., Qin, X., Chen, Y., & Hu, J. (2017). Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model. Biochemical Pharmacology, 140, 115-123. https://doi.org/10.1016/j.bcp.2017.05.017
Liu Y, et al. Wnt/β-catenin Signaling Plays an Essential Role in Α7 Nicotinic Receptor-mediated Neuroprotection of Dopaminergic Neurons in a Mouse Parkinson's Disease Model. Biochem Pharmacol. 2017 09 15;140:115-123. PubMed PMID: 28551099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model. AU - Liu,Yuan, AU - Hao,Shuai, AU - Yang,Beibei, AU - Fan,Yi, AU - Qin,Xiaodong, AU - Chen,Yun, AU - Hu,Jun, Y1 - 2017/05/25/ PY - 2017/04/22/received PY - 2017/05/22/accepted PY - 2017/5/30/pubmed PY - 2017/8/19/medline PY - 2017/5/29/entrez KW - Alpha7 nicotinic receptors KW - Dopamine KW - Knockout KW - Mouse KW - Parkinson’s disease KW - Wnt signaling pathway SP - 115 EP - 123 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 140 N2 - Parkinson's disease (PD) is a neurodegenerative disorder with an incidence second only to Alzheimer's disease. The main pathological feature of PD is the death of dopaminergic neurons in the substantia nigra pars compacta. Nicotinic receptor agonists are neuroprotective in several PD models and there is considerable evidence that α7 nicotinic acetylcholine receptors (α7-nAChRs) are important therapeutic targets for neurodegenerative diseases. However, the involvement of α7-nAChRs and underlying signaling mechanisms in PD pathogenesis are unclear. The objective of the present study was to explore the potential functions of α7-nAChRs in PD pathology, and to determine whether these effects are exerted via Wnt/β-catenin signaling in a mouse PD model. In the in vivo study, α7-nAChR knockout (α7-KO) reversed the beneficial effects of nicotine on motor deficits, dopaminergic neuron loss, astrocyte and microglia activation, and reduced striatal dopamine release induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Injury to SH-SY5Y cells by 1-methyl-4-phenylpyridinium treatment was also ameliorated by nicotine, and this effect was abolished by methyllycaconitine (MLA), a selective α7-nAChR antagonist, or by siRNA-mediated α7-nAChR knockdown. Furthermore, nicotine increased expression levels of Wnt/β-catenin signaling proteins in the PD mouse model or in the SH-SY5Y cells treated by 1-methyl-4-phenylpyridinium, and these effects were also reversed by MLA or α7-siRNA treatment in vivo or in vitro. These results suggest that endogenous α7-nAChR mechanisms play a crucial role in a mouse PD model via regulation of Wnt/β-catenin signaling. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/28551099/Wnt/β_catenin_signaling_plays_an_essential_role_in_α7_nicotinic_receptor_mediated_neuroprotection_of_dopaminergic_neurons_in_a_mouse_Parkinson's_disease_model_ DB - PRIME DP - Unbound Medicine ER -