Melatonin in mitochondrial dysfunction and related disorders

• Autores: Srinivasan, Venkataramanujan; Spence, David Warren; Pandi Perumal, Seithikurippu R.; Brown, Gregory M.; Cardinali, Daniel Pedro
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: International Journal of Alzheimer's Disease. 2011
• Materia: MELATONINA; RECEPTORES DE MELATONINA; FUNCION MITOCONDRIAL; ENFERMEDADES NEUROGENERATIVAS
• Institución: Pontificia Universidad Católica Argentina

Fil: Srinivasan, Venkataramanujan. Sri Sathya Sai Medical Educational and Research Foundation; India
Fil: Spence, David Warren. Instituto Canadiense del Sueño; Canadá
Fil: Pandi Perumal, Seithikurippu R. Somnogen Inc; Canadá
Fil: Brown, Gregory M. Centro de Adicciones y Salud Mental; Canadá
Fil: Cardinali, Daniel P. Pontifcia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Cardinali, Daniel P. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina
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, enhancedNOproduction, 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.