title: Melatonin regulates the autophagic flux via activation of alpha-7 nicotinic acetylcholine receptors.
abstract: Our previous study suggested that melatonin-mediated neuroprotective effects are related with the activation of autophagy. However, the mechanism of melatonin-mediated autophagic activation in prion-mediated mitochondrial damage is not reported. Alpha-7 nicotinic acetylcholine receptors (α7nAchR) is a member of nicotinic acetylcholine receptors, and α7nAchR activation regulates via melatonin. Thus, we hypothesized that melatonin-mediated neuroprotective effect related with to autophagy pathway as a result of α7nAchR regulation. Inactivation of α7nAchR inhibited melatonin-mediated autophagic activation and protective effect against prion-mediated mitochondrial neurotoxicity. Also, knockdown of ATG5 blocked the melatonin-mediated neuroprotection and did not influence to the activation of α7nAchR caused by melatonin. This report is the first study demonstrating that melatonin-mediated autophagic activation regulates via modulation of α7nAchR signals, and upregulation of α7nAchR signals induced by melatonin plays a pivotal role in neuroprotection of prion-mediated mitochondrial neurotoxicity. Our results suggested that regulator of α7 nAChR signals including melatonin may have used for neuroprotective strategies for the neurodegenerative disorders including prion 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: D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D034622:RNA Interference; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D011978:Receptors, Nicotinic; D008550:Melatonin
keywords: alpha-7 nicotinic receptor; autophagy flux; melatonin; prion