ABSTRACT
Melatonin (N-acetyl-5-methoxytryptamine) is a natural hormone secreted by the pineal gland and other tissues of mammals, as well as plants (Dubbels et al., 1995; Esposito and Cuzzocrea, 2010). In clinical use for many years, melatonin is safe and well-tolerated even at high doses (Weishaupt et al., 2006) and easily crosses the blood-brain barrier. Besides being used to increase sleep efciency, treat jet lag, improve the cardiovascular system (Sewerynek, 2002), as an antiaging drug (GutierrezCuesta et al., 2008), and as a dietary supplement and cancer-protective hormone (Ravindra et al., 2006), intensive research in the past roughly 15 years has indicated melatonin’s benecial effects in the experimental models of neurodegenerative diseases. In particular, its broad spectrum of antioxidant activities in many neurodegenerative diseases (Tan et al., 2002) of the central nervous system (CNS) has been well documented and reviewed (Reiter et al., 1999). This small amphiphilic molecule, a powerful antioxidant and free-radical scavenger, directly scavenges hydroxyl, carbonate, and reactive nitrogen species as well as various organic radicals (Pandi-Perumal et al., 2013; Reiter et al., 2010) and enhances the antioxidant potential of the cell by stimulating the activity of superoxide
10.1 Introduction .......................................................................................................................... 111 10.1.1 Melatonin May Be Benecial in the Treatment of Neurodegenerative Diseases ..... 111 10.1.2 Intrinsic and Extrinsic Apoptotic Pathways in Neurodegenerative Diseases ........... 112 10.1.3 Survival Signaling Pathways in Neurodegenerative Diseases .................................. 116
10.2 Melatonin in Neurodegenerative Diseases ........................................................................... 117 10.2.1 Melatonin in Parkinson’s Disease ............................................................................. 117 10.2.2 Melatonin in Alzheimer’s Disease ............................................................................ 120 10.2.3 Melatonin in Amyotrophic Lateral Sclerosis ............................................................ 121 10.2.4 Melatonin in Huntington’s Disease........................................................................... 122
10.3 Conclusion and Perspective .................................................................................................. 123 Acknowledgments ..........................................................................................................................124 References ......................................................................................................................................124
