Melatonin Beyond Its Classical Functions

Hardeland, Rüdiger; Pöeggeler, Burkhard

doi:10.2174/1874360900801010001

Cited by 27 publications

(52 citation statements)

References 345 publications

(520 reference statements)

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“…In fact, it is assumed that serotonin is an intermediate in the synthesis of melatonin in Saccharomyces cerevisiae , as it is in vertebrates [28, 60]. …”

Section: Synthesis Of Other Bioactive Compounds From Aromatic Aminmentioning

confidence: 99%

Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

Mas

Guillamón

Torija

et al. 2014

BioMed Research International

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Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

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“…In fact, it is assumed that serotonin is an intermediate in the synthesis of melatonin in Saccharomyces cerevisiae , as it is in vertebrates [28, 60]. …”

Section: Synthesis Of Other Bioactive Compounds From Aromatic Aminmentioning

confidence: 99%

Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

Mas

Guillamón

Torija

et al. 2014

BioMed Research International

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“…Ramelteon displays no relevant antioxidant capacity in the ABTS radical cation assay, as compared to luzindole or melatonin [150]. However, MT 1 /MT 2 receptor-mediated effects on the upregulation of several antioxidant enzymes by physiological concentration of melatonin [151] such as glutathione peroxidase, glutathione reductase, γ -glutamylcysteine synthase, glucose-6-phosphate dehydrogenase, hemoperoxidase/catalase, Cu,Zn- and Mn-superoxide dismutases (reviewed in [152–155] can well give the basis for the use of ramelteon in AD. Since there are extensive data indicating a loss of melatonin receptors in AD patients, including the cerebral cortex and pineal gland (MT 1 and MT 2 receptors) [156], the hippocampus [157] and retina [158] (MT 2 receptors) and the cerebrovascular system [159], and SCN [126, 128] (MT 1 receptors), the chances of alleviating symptoms such as sundowning and disturbed sleep by giving the MT 1 /MT 2 receptor agonist may vanish in late AD patients.…”

Section: Use Of Melatonin Agonist Ramelteon In Admentioning

confidence: 99%

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

Srinivasan

Kaur

Pandi-Perumal³

et al. 2010

International Journal of Alzheimer's Disease

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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.

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“…Whether or not these conclusions on direct or secondary inductions by melatonin or melatonin-mediated changes in the redox balance may also apply to the upregulation of several other antioxidant enzymes, remains to be clarified. This would especially concern γ-glutamylcysteine synthase, glucose-6-phosphate dehydrogenase, Cu,Zn- and Mn-superoxide dismutases and hemoperoxidase/catalase (reviewed in [1,75–77]).…”

Section: Chronobiological Effects Of Melatonin Outside the Scnmentioning

confidence: 99%

Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction

Hardeland

2013

IJMS

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The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases.

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Melatonin Beyond Its Classical Functions

Cited by 27 publications

References 345 publications

Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

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

Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction

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