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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 741974, 15 pages
http://dx.doi.org/10.4061/2011/741974
Review Article

Melatonin and Its Agonist Ramelteon in Alzheimer's Disease: Possible Therapeutic Value

1Sri Sathya Sai Medical Educational and Research Foundation, Prasanthi Nilayam, 40- Kovai Thirunagar, Coimbatore 641014, India
2Department of Physiology, Faculty of Medicine, Karpagam University, Eachanari, Coimbatore 641021, India
3Department of Anatomy, Yong Loo Lin School of Medicine, Block MD10, Medical Drive, National University of Singapore, Singapore 117597
4Somnogen Inc., College Street, Toronto, ON, Canada M6H 1C5
5Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada M5T 1RS
6Departmento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina, Avenida Alicia Moreau de Justo 1500, 4° piso, 1107 Buenos Aires, Argentina

Received 21 September 2010; Revised 8 October 2010; Accepted 27 October 2010

Academic Editor: Anthony R. White

Copyright © 2011 Venkatramanujam Srinivasan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by the progressive loss of cognitive function, loss of memory and insomnia, and abnormal behavioral signs and symptoms. Among the various theories that have been put forth to explain the pathophysiology of AD, the oxidative stress induced by amyloid β-protein (Aβ) deposition has received great attention. Studies undertaken on postmortem brain samples of AD patients have consistently shown extensive lipid, protein, and DNA oxidation. Presence of abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation all have been demonstrated in neural tissues of AD patients. Moreover, AD patients exhibit severe sleep/wake disturbances and insomnia and these are associated with more rapid cognitive decline and memory impairment. On this basis, the successful management of AD patients requires an ideal drug that besides antagonizing Aβ-induced neurotoxicity could also correct the disturbed sleep-wake rhythm and improve sleep quality. Melatonin is an effective chronobiotic agent and has significant neuroprotective properties preventing Aβ-induced neurotoxic effects in a number of animal experimental models. Since melatonin levels in AD patients are greatly reduced, melatonin replacement has the potential value to be used as a therapeutic agent for treating AD, particularly at the early phases of the disease and especially in those in whom the relevant melatonin receptors are intact. As sleep deprivation has been shown to produce oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, and altered proteosomal processing with abnormal activation of enzymes, treatment of sleep disturbances may be a priority for arresting the progression of AD. In this context the newly introduced melatonin agonist ramelteon can be of much therapeutic value because of its highly selective action on melatonin MT1/MT2 receptors in promoting sleep.