دانلود رایگان مقاله انگلیسی ملاتونین به عنوان یک تنظیم کننده ی درونی بیماری ها: نقش خودخواری - الزویر 2018

Abstract:

Melatonin has long been known for its apparent effects on sleep and circadian rhythm. It may participate as a possible therapeutic agent in neurodegenerative, cardiovascular, and endocrine disorders as well. Autophagy is a lysosomal degradation process that occurs in response to starvation and other stresses. Recent studies have reported that melatonin may modulate the autophagy process. We reviewed the current literature that has reported on how different diseases and/or experimental models change autophagy parameters. We also discussed the effect of melatonin on autophagy parameters in the central nervous, cardiovascular, gastrointestinal and endocrine systems as reported in nonclinical studies. Moreover, the molecular targets for melatonin are discussed in details. In summary, melatonin has been reported to enhance significant protective effects in different in vitro and in vivo studies either through enhancement or inhibition of the autophagy process. Melatonin holds promise in the treatment of several major diseases. Regulation of autophagy by melatonin is a determinant parameter that should be considered in the future studies.

Conclusion and perspectives

Melatonin is potentially a very important drug candidate. A growing number of articles continues to be published in the peer reviewed literature that support the beneficial effects of melatonin. Activation or inhibition of melatonin signaling is a novel area to consider as a potential therapeutic approach for treating some important diseases including neurodegenerative diseases. On the other hand, there can be little doubt that autophagy has a crucial role in homeostasis and in human diseases. A large number of molecules are under evaluations in drug development for treatment of cancer and neurodegenerative disease. In the present paper, some of the significant protective and beneficial effects of melatonin have been reviewed. Melatonin appears to induce its beneficial effects through autophagy promotion and/or autophagy suppression. This finding confirms the double role of autophagy in cells and implies that melatonin can balance the autophagy process. This balance is, at least in part, responsible for the protective role of melatonin in the central nervous, cardiovascular, endocrine and gastrointestinal systems. As presented in figure 1, melatonin through very different mechanism, activates or inhibits the autophagy process, suggesting that melatonin give us the opportunity to change the function of different organs by autophagy. Melatonin also has significant antioxidant and anti-apoptotic effects. Besides activation of classical MT1 and MT2 receptors, activation of RORα by melatonin is another alternative receptor and an important target for melatonin that should be considered in future studies. Development and the successful use of the selective MT1 and MT2 receptors agonists for treatment of sleep disorders open the opportunity to use these drugs in the treatment of diseases other than insomnia with limited side effects. Moreover, its synergistic effects with other molecules including valproate indicate that melatonin in combination with other therapeutic agents may elicit better therapeutic responses with lower toxicities. This review offers a new look at melatonin and its potential therapeutic effects through its effects on autophagy. Melatonin should be given serious consideration in the future.