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Open Access Highly Accessed Review

Melatonin in Alzheimer's disease and other neurodegenerative disorders

V Srinivasan1, SR Pandi-Perumal2, DP Cardinali3, B Poeggeler4 and R Hardeland4*

Author Affiliations

1 Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kampus Kesihatan, 16150, Kubang kerian, Kelantan, Malaysia

2 Comprehensive Center for Sleep Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, 1176 – 5th Avenue, New York, NY 10029, USA

3 Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, 1121, Buenos Aires, Argentina

4 Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Berliner Str. 28, D-37073 Goettingen, Germany

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Behavioral and Brain Functions 2006, 2:15  doi:10.1186/1744-9081-2-15

Published: 4 May 2006

Abstract

Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-β toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin, its analogues and kynuric metabolites may have potential value in prevention and treatment of AD and other neurodegenerative disorders.