ABSTRACT

Dementia affects 35 million people worldwide, and this total is predicted to increase to over 60 million people in 2030 and over 100 million people by 2050. Due to this sharp increase in prevalence and the high cost for healthcare for these individuals, treatments that prevent or even delay the

27.1 Alzheimer’s Disease ............................................................................................................ 353 27.2 Mitochondrial Dysfunction as a Contributing Factor in AD .............................................. 354 27.3 Melatonin Protects Mitochondrial, Cell, and Brain Function in AD Mice in Many Ways .....356 27.4 Melatonin Receptors ........................................................................................................... 356 27.5 Melatonin Receptors and the Hippocampus ....................................................................... 357 27.6 Mitochondrial Localization of the MT1 Melatonin Receptor in Mice ............................... 357 27.7 AD Patients Have Decreased Melatonin Levels ................................................................. 358 27.8 Changes in Melatonin Receptor Levels in Aging, Parkinson’s Disease, and AD .............. 358 27.9 Melatonin Treatment Has Shown Benecial Effects in AD Patients ................................. 358 27.10 Benecial Effects of Melatonin in Cell and Mouse Models of AD .................................... 359

27.10.1 Indole-3-Propionamide as an Alternative to Melatonin for the Treatment of Neurodegenerative Disease ................................................................................... 359

27.10.2 Direct Effects of Melatonin and IPAM on Mitochondrial Function .....................360 27.11 Antioxidant Signaling through Melatonin Receptors .........................................................360 27.12 Melatonin Receptor Agonists for the Treatment of AD ...................................................... 361 27.13 Role that Melatonin Receptors Play in Protecting AD-Associated Mitochondrial

Dysfunction ......................................................................................................................... 361 27.14 Role That Melatonin Receptors Play in Protecting from Aging-Induced Loss of

Cytochrome c Oxidase Activity in Mice ............................................................................ 362 27.15 Role That Melatonin Receptors Play in Protecting from AD-Induced Alteration of

COX Activity in Mice ......................................................................................................... 362 27.16 Molecular Mechanisms through Which Melatonin Receptor Signaling Protects

Mitochondrial Function in Aging and Disease ................................................................... 363 27.17 Conclusion ........................................................................................................................... 365 Acknowledgments .......................................................................................................................... 365 References ...................................................................................................................................... 365

onset of dementia are highly sought. In this regard, melatonin has been identied as a compound that may delay the onset of certain types of dementia. In this chapter, we will discuss the potential of melatonin as a treatment for Alzheimer’s disease (AD), the most prevalent form of dementia, and the role that melatonin and its cellular receptors play in this process.