Empowering Melatonin Therapeutics with Models

Overview

Journal Diseases

Date 2021 Oct 26

PMID 34698120

Citations 5

Authors

Cassandra Millet-Boureima

Caroline C Ennis

Jurnee Jamison

Shana McSweeney

Anna Park

Chiara Gamberi

Affiliations

Soon will be listed here.

Abstract

Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases.

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References

Kenyon C . The genetics of ageing. Nature. 2010; 464(7288):504-12. DOI: 10.1038/nature08980. View

Ma H, Kang J, Fan W, He H, Huang F . ROR: Nuclear Receptor for Melatonin or Not?. Molecules. 2021; 26(9). PMC: 8124216. DOI: 10.3390/molecules26092693. View

Onuki J, Almeida E, Medeiros M, Di Mascio P . Inhibition of 5-aminolevulinic acid-induced DNA damage by melatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, quercetin or resveratrol. J Pineal Res. 2005; 38(2):107-15. DOI: 10.1111/j.1600-079X.2004.00180.x. View

Kosar P, Naziroglu M, Ovey I, Cig B . Synergic Effects of Doxorubicin and Melatonin on Apoptosis and Mitochondrial Oxidative Stress in MCF-7 Breast Cancer Cells: Involvement of TRPV1 Channels. J Membr Biol. 2015; 249(1-2):129-40. DOI: 10.1007/s00232-015-9855-0. View

Reiter R . Melatonin: Lowering the High Price of Free Radicals. News Physiol Sci. 2001; 15:246-250. DOI: 10.1152/physiologyonline.2000.15.5.246. View

Kalsbeek A, Buijs R . Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting. Cell Tissue Res. 2002; 309(1):109-18. DOI: 10.1007/s00441-002-0577-0. View

Jenwitheesuk A, Nopparat C, Mukda S, Wongchitrat P, Govitrapong P . Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways. Int J Mol Sci. 2014; 15(9):16848-84. PMC: 4200827. DOI: 10.3390/ijms150916848. View

Hely M, Morris J, Reid W, Trafficante R . Sydney Multicenter Study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2004; 20(2):190-9. DOI: 10.1002/mds.20324. View

Sohal R, Brunk U . Mitochondrial production of pro-oxidants and cellular senescence. Mutat Res. 1992; 275(3-6):295-304. DOI: 10.1016/0921-8734(92)90033-l. View

10.

Vasiliou V, Ross D, Nebert D . Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family. Hum Genomics. 2006; 2(5):329-35. PMC: 3500182. DOI: 10.1186/1479-7364-2-5-329. View

11.

Margheri M, Pacini N, Tani A, Nosi D, Squecco R, Dama A . Combined effects of melatonin and all-trans retinoic acid and somatostatin on breast cancer cell proliferation and death: molecular basis for the anticancer effect of these molecules. Eur J Pharmacol. 2012; 681(1-3):34-43. DOI: 10.1016/j.ejphar.2012.02.011. View

12.

Liu J, Clough S, Hutchinson A, Adamah-Biassi E, Popovska-Gorevski M, Dubocovich M . MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective. Annu Rev Pharmacol Toxicol. 2015; 56:361-83. PMC: 5091650. DOI: 10.1146/annurev-pharmtox-010814-124742. View

13.

Ayoub M, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M . Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer. J Biol Chem. 2002; 277(24):21522-8. DOI: 10.1074/jbc.M200729200. View

14.

Carrillo-Vico A, Lardone P, Fernandez-Santos J, Martin-Lacave I, Calvo J, Karasek M . Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J Clin Endocrinol Metab. 2004; 90(2):992-1000. DOI: 10.1210/jc.2004-1429. View

15.

Margulis L . Symbiotic theory of the origin of eukaryotic organelles; criteria for proof. Symp Soc Exp Biol. 1975; (29):21-38. View

16.

Martin H, Teismann P . Glutathione--a review on its role and significance in Parkinson's disease. FASEB J. 2009; 23(10):3263-72. DOI: 10.1096/fj.08-125443. View

17.

Fisher S, Sugden D . Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle. Sleep. 2010; 33(6):833-40. PMC: 2881717. DOI: 10.1093/sleep/33.6.833. View

18.

Millet-Boureima C, Rozencwaig R, Polyak F, Gamberi C . Cyst Reduction by Melatonin in a Novel Model of Polycystic Kidney Disease. Molecules. 2020; 25(22). PMC: 7700119. DOI: 10.3390/molecules25225477. View

19.

Weekley L . Effects of melatonin on pulmonary and coronary vessels are exerted through perivascular nerves. Clin Auton Res. 1993; 3(1):45-7. DOI: 10.1007/BF01819143. View

20.

Carrillo-Vico A, Reiter R, Lardone P, Herrera J, Fernandez-Montesinos R, Guerrero J . The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs. 2006; 7(5):423-31. View