| First Author | Liu Y | Year | 2017 |
| Journal | Biochem Pharmacol | Volume | 140 |
| Pages | 115-123 | PubMed ID | 28551099 |
| Mgi Jnum | J:252635 | Mgi Id | MGI:6107326 |
| Doi | 10.1016/j.bcp.2017.05.017 | Citation | Liu Y, et al. (2017) Wnt/beta-catenin signaling plays an essential role in alpha7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model. Biochem Pharmacol 140:115-123 |
| abstractText | 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 alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs) are important therapeutic targets for neurodegenerative diseases. However, the involvement of alpha7-nAChRs and underlying signaling mechanisms in PD pathogenesis are unclear. The objective of the present study was to explore the potential functions of alpha7-nAChRs in PD pathology, and to determine whether these effects are exerted via Wnt/beta-catenin signaling in a mouse PD model. In the in vivo study, alpha7-nAChR knockout (alpha7-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 alpha7-nAChR antagonist, or by siRNA-mediated alpha7-nAChR knockdown. Furthermore, nicotine increased expression levels of Wnt/beta-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 alpha7-siRNA treatment in vivo or in vitro. These results suggest that endogenous alpha7-nAChR mechanisms play a crucial role in a mouse PD model via regulation of Wnt/beta-catenin signaling. |
