Melatonin : a pleiotropic, orchestrating regulator molecule

• Autores: Srinivasan, Venkataramanujan; Pandi Perumal, Seithikurippu R.; Brown, Gregory M.; Cardinali, Daniel Pedro; Spence, David Warren; Hardeland, Rüdiger
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Progress in Neurobiology. 2011, 93
• Materia: MELATONINA; SUEÑO; ENVEJECIMIENTO; DIABETES; MITOCONDRIOS; RITMO CIRCADIANO
• Institución: Pontificia Universidad Católica Argentina

Fil: Srinivasan, Venkataramanujan. Sri Sathya Sai Medical Educational and Research Foundation; India
Fil: Srinivasan, Venkataramanujan. Karpagam University. Facultad de Medicina. Departamento de Fisiología; India
Fil: Pandi Perumal, Seithikurippu R. Somnogen Inc; Canadá
Fil: Brown, Gregory M. Universidad de Toronto. Facultad de Medicina. Departamento de Psiquiatría; Canadá
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina
Fil: Spence, David Warren. Investigador independiente; Canadá
Fil: Hardeland, Rüdiger. Universidad de Goettingen. Insituto Johann Friedrich Blumenbach de Zoología y Antropología; Alemania
Abstract: Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitment of downstream factors, including various kinases, transcription factors and ion channels. Additional actions via nuclear receptors and other binding sites are likely. By virtue of high receptor density in the circadian pacemaker, melatonin is involved in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts effects on peripheral oscillators, including phase coupling of parallel cellular clocks based on alternate use of core oscillator proteins. Direct central and peripheral actions concern the up- or downregulation of various proteins, among which inducible and neuronal NO synthases seem to be of particular importance for antagonizing inflammation and excitotoxicity. The methoxyindole is also synthesized in several peripheral tissues, so that the total content of tissue melatonin exceeds by far the amounts in the circulation. Emerging fields in melatonin research concern receptor polymorphism in relation to various diseases, the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and insulin resistance, and mitochondrial effects. Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging. Newly discovered influences on sirtuins and downstream factors indicate that melatonin has a role in mitochondrial biogenesis.