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- Title
Remarkable impairment of Wnt/β-catenin signaling in the brains of the mice infected with scrapie agents.
- Authors
Sun, Jing; Wang, Hui; Chen, Li‐Na; Wang, Jing; Lv, Yan; Yang, Xiao‐Dong; Zhang, Bao‐Yun; Tian, Chan; Shi, Qi; Dong, Xiao‐Ping
- Abstract
Prion diseases are a group of neurodegenerative diseases characterized by neuronal loss and spongiform degeneration, astrogliosis and aggregation of scrapie prion protein (PrPSc) in the central nervous system ( CNS). The Wnt signaling pathway is a highly evolutionarily conserved pathway in eukaryotes that regulates cell proliferation, differentiation and survival. Impairment of Wnt/β-catenin signaling has been reported in the CNS of various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. To investigate the functional state of Wnt/β-catenin signaling in the CNS tissues during the progression of prion disease, the components of Wnt/β-catenin signaling in the brains of the scrapie agents 139A- and ME7-infected mice were evaluated. Compared with the normal controls, the brain levels of phosphor-β-catenin (Ser33,37 and Thr41) in 139A- and ME7-infected mice were significantly increased, while those of cyclin D1, which is one of the target genes of Wnt signaling, were decreased. The levels of phosphor-glycogen synthase kinase-3β ( GSK-3β) Ser9 were markedly reduced, representing an enhanced GSK-3β activity in scrapie-infected mice. Both western blot and immunohistochemical assays revealed a remarkable increase of Dickkopf-1, the antagonist of Wnt/β-catenin signaling, in the brains of scrapie-infected anim-als, which co-localized well with the remaining neurons in the immunofluorescent tests. We also observed slightly decreased Wnt-3 and unchanged disheveled-3 (Dvl-3) in the brains of the infected mice. Our data, here, strongly indicate an impairment of Wnt/β-catenin pathway in the brains of prion disease, which shows a time-dependent progression along with the incubation period.
- Subjects
WNT proteins; CATENINS; CELLULAR signal transduction; TREATMENT of scrapie; CYCLIN-dependent kinases
- Publication
Journal of Neurochemistry, 2016, Vol 136, Issue 4, p731
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13416