Table of Contents Author Guidelines Submit a Manuscript
International Journal of Alzheimer’s Disease
Volume 2011, Article ID 326320, 16 pages
http://dx.doi.org/10.4061/2011/326320
Review Article

Melatonin in Mitochondrial Dysfunction and Related Disorders

1Sri Sathya Sai Medical, Educational and Research Foundation, Prashanthi Nilayam 40, Kovai Thirunagar Coimbatore 641014, India
2323 Brock Avenue, Toronto, ON, Canada M6K 2M6
3Somnogen Inc., College Street, Toronto, ON, Canada M6H 1C5
4Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8
5Departamento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina, Avenida Alicia Moreau de Justo 1500, 4° Piso, 1107 Buenos Aires, Argentina
6Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina

Received 28 November 2010; Accepted 2 March 2011

Academic Editor: B. J. Bacskai

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

Mitochondrial dysfunction is considered one of the major causative factors in the aging process, ischemia/reperfusion (I/R), septic shock, and neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity, enhanced NO production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pore all have been suggested as factors responsible for impaired mitochondrial function. Melatonin, the major hormone of the pineal gland, also acts as an antioxidant and as a regulator of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective for preventing oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. In addition, melatonin is known to retard aging and to inhibit the lethal effects of septic shock or I/R lesions by maintaining respiratory complex activities, electron transport chain, and ATP production in mitochondria. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other antioxidants. Melatonin has thus emerged as a major potential therapeutic tool for treating neurodegenerative disorders such as PD or AD, and for preventing the lethal effects of septic shock or I/R.