Neuroprotective effect of cellular prion protein (PrPC) is related with activation of alpha7 nicotinic acetylcholine receptor (alpha 7nAchR)-mediated autophagy flux

作者：Jeong Jae Kyo; Park Sang Youel^*

来源：Oncotarget, 2015, 6(28): 24660-24674.

DOI：10.18632/oncotarget.4953

• autophagy flux
• alpha-7 nicotinic receptor
• prpc
• prion
• Geotarget

Activation of the alpha7 nicotinic acetylcholine receptor (alpha 7nAchR) is regulated by prion protein (PrPC) expression and has a neuroprotective effect by modulating autophagic flux. In this study, we hypothesized that PrPC may regulate alpha 7nAchR activation and that may prevent prion-related neurodegenerative diseases by regulating autophagic flux. PrP(106-126) treatment decreased alpha 7nAchR expression and activation of autophagic flux. In addition, the alpha 7nAchR activator PNU-282987 enhanced autophagic flux and protected neuron cells against PrP(106-126)-induced apoptosis. However, activation of autophagy and the protective effects of PNU-282987 were inhibited in PrPC knockout hippocampal neuron cells. In addition, PrPC knockout hippocampal neuron cells showed decreased alpha 7nAchR expression levels. Adenoviral overexpression of PrPC in PrPC knockout hippocampal neuron cells resulted in activation of autophagic flux and inhibition of prion peptide-mediated cell death via alpha 7nAchR activation. This is the first report demonstrating that activation of alpha 7nAch-Rmediated autophagic flux is regulated by PrPC, and that activation of alpha 7nAchR regulated by PrPC expression may play a pivotal role in protection of neuron cells against prion peptide-induced neuron cell death by autophagy. These results suggest that alpha 7nAchR-mediated autophagic flux may be involved in the pathogenesis of prion-related diseases and may be a therapeutic target for prion-related neurodegenerative diseases.

• 出版日期2015-9-22