Melatonin regulates the autophagic flux via activation of alpha-7 nicotinic acetylcholine receptors

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 (7nAchR) is a member of nicotinic acetylcholine receptors, and 7nAchR activation regulates via melatonin. Thus, we hypothesized that melatonin-mediated neuroprotective effect related with to autophagy pathway as a result of 7nAchR regulation. Inactivation of 7nAchR 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 7nAchR caused by melatonin. This report is the first study demonstrating that melatonin-mediated autophagic activation regulates via modulation of 7nAchR signals, and upregulation of 7nAchR signals induced by melatonin plays a pivotal role in neuroprotection of prion-mediated mitochondrial neurotoxicity. Our results suggested that regulator of 7nAChR signals including melatonin may have used for neuroprotective strategies for the neurodegenerative disorders including prion diseases.