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Melatonin regulates the autophagic flux via activation of alpha‐7 nicotinic acetylcholine receptors
Author(s) -
Jeong JaeKyo,
Park SangYouel
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12235
Subject(s) - melatonin , neuroprotection , neurotoxicity , autophagy , melatonin receptor , nicotinic acetylcholine receptor , chemistry , receptor , nicotinic agonist , biology , microbiology and biotechnology , pharmacology , neuroscience , biochemistry , apoptosis , organic chemistry , toxicity
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 ( α 7nAchR) is a member of nicotinic acetylcholine receptors, and α 7nAchR activation regulates via melatonin. Thus, we hypothesized that melatonin‐mediated neuroprotective effect related with to autophagy pathway as a result of α 7nAchR regulation. Inactivation of α 7nAchR inhibited melatonin‐mediated autophagic activation and protective effect against prion‐mediated mitochondrial neurotoxicity. Also, knockdown of ATG 5 blocked the melatonin‐mediated neuroprotection and did not influence to the activation of α 7nAchR caused by melatonin. This report is the first study demonstrating that melatonin‐mediated autophagic activation regulates via modulation of α 7nAchR signals, and upregulation of α 7nAchR signals induced by melatonin plays a pivotal role in neuroprotection of prion‐mediated mitochondrial neurotoxicity. Our results suggested that regulator of α 7 nAChR signals including melatonin may have used for neuroprotective strategies for the neurodegenerative disorders including prion diseases.