title: Neuroprotective effect of cellular prion protein (PrPC) is related with activation of alpha7 nicotinic acetylcholine receptor (α7nAchR)-mediated autophagy flux.
abstract: Activation of the alpha7 nicotinic acetylcholine receptor (α7nAchR) 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 α7nAchR activation and that may prevent prion-related neurodegenerative diseases by regulating autophagic flux. PrP(106-126) treatment decreased α7nAchR expression and activation of autophagic flux. In addition, the α7nAchR 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 α7nAchR 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 α7nAchR activation. This is the first report demonstrating that activation of α7nAchR-mediated autophagic flux is regulated by PrPC, and that activation of α7nAchR 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 α7nAchR-mediated autophagic flux may be involved in the pathogenesis of prion-related diseases and may be a therapeutic target for prion-related neurodegenerative diseases.
authors: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea.|Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University, Jeonju, Korea.
authors: Jae-Kyo
authors: JK
authors: Jeong
authors: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea.|Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University, Jeonju, Korea.
authors: Sang-Youel
authors: SY
authors: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D005838:Genotype; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010641:Phenotype; D018621:PrPC Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: C579166:Chrna7 protein, mouse; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D010446:Peptide Fragments; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D064569:alpha7 Nicotinic Acetylcholine Receptor; C082632:prion protein (106-126)
keywords: Geotarget; PrPC; alpha-7 nicotinic receptor; autophagy flux; prion