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Melatonina e triptofano: a modulação bioquímica na qualidade do sono
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Resumo(s)
A melatonina é habitualmente definida como o produto de secreção da glândula pineal, formada a partir do aminoácido essencial triptofano. Para além de ser a chave do ritmo circadiano e controlar o ciclo sono-vigília, a melatonina também está envolvida nos processos anti-inflamatórios, anti-oxidantes, sistema imune, regulação da pressão sanguínea e atividade cerebral.
Distúrbios do sono e do ciclo circadiano são manifestações comuns de diversas patologias do foro neuropsicológico, e podem agravar a progressão das mesmas. Recentemente reconheceu-se um ciclo vicioso entre o desenvolvimento de inflamação crónica e os distúrbios do sono que podem provocar défice de melatonina. Um desequilíbrio na regulação e processos metabólicos que envolvem o triptofano, pode potenciar a via das quinureninas e diminuir a via da serotonina. Estas alterações podem diminuir a produção de melatonina e induzir um aumento das quinureninas neuroativas que poderão ter efeito neurotóxico e aumentar a inflamação. Devido aos seus efeitos fisiológicos, o défice de melatonina tem sido associado ao desenvolvimento de patologias neuropsiquiátricas, por deixar o sistema nervoso central desprotegido das espécies reativas, que vão favorecer o stress oxidativo e a neuroinflamação.
Esta monografia pretende rever os principais trabalhos de investigação que salientam a importância das vias metabólicas do triptofano e a forma como se associam aos mecanismos fisiopatológicos. O seu âmbito inclui ainda os dados científicos que evidenciam a relevância da administração de melatonina, ou do seu precursor triptofano, uma vez que são moléculas com relativa segurança, na intervenção terapêutica de algumas doenças neuropsicológicas. O objetivo desta suplementação visa melhorar a qualidade do sono, atenuar o desenvolvimento e progressão da doença e aliviar os seus sintomas. No entanto, a dose utilizada deve ser adequada a cada individuo, sendo por isso necessários melhores estudos no sentido de diminuir a administração empírica e adequar a terapêutica, melhorando a sua segurança e uso racional.
Melatonin is well-defined as the secretory product of the pineal gland, synthetized from the essential amino acid tryptophan. This signaling molecule is the key to circadian rhythm, but melatonin could also control the sleep-awake rhythm, exert anti- inflammatory effects, scavenge free radical species, enhance the immune system, regulate the blood pressure and the neural development. Sleep disorders and disrupted circadian rhythm are common signs of some neuropsychological pathologies, and they can enhance the progression of these disabilities. Recently, a vicious cycle has been recognized between the development of chronic inflammation and sleep disorders that can induce melatonin deficit. Due to tryptophan metabolism dysregulation, the kynurenine pathway may be induced and the serotonin pathway decreased. This may lead to a decreased production of melatonin and on the other hand will increase neuroactive kynurenines that may have a neurotoxic effect and increase inflammation. Considering its crucial physiological effects, melatonin deficiency has been linked to the development of neurological and psychological diseases, by letting the central nervous system unprotected from reactive species that will favor oxidative stress and neuroinflammation. This review will give new insights on the balance between the two tryptophan metabolic pathways and how they are associated with pathophysiological mechanisms. In addition, this work assesses the relevance of melatonin administration, or its precursor tryptophan, since they are relatively safe molecules, as potential therapeutic interventions of some neuropsychological diseases. The aim of this supplementation is to improve the quality of sleep, diminish the development and progression of the disease and relieve symptoms. However, it is important to adapt the dose for each individual, so further studies are needed in order to avoid empirical administration, improving safety and its rational use.
Melatonin is well-defined as the secretory product of the pineal gland, synthetized from the essential amino acid tryptophan. This signaling molecule is the key to circadian rhythm, but melatonin could also control the sleep-awake rhythm, exert anti- inflammatory effects, scavenge free radical species, enhance the immune system, regulate the blood pressure and the neural development. Sleep disorders and disrupted circadian rhythm are common signs of some neuropsychological pathologies, and they can enhance the progression of these disabilities. Recently, a vicious cycle has been recognized between the development of chronic inflammation and sleep disorders that can induce melatonin deficit. Due to tryptophan metabolism dysregulation, the kynurenine pathway may be induced and the serotonin pathway decreased. This may lead to a decreased production of melatonin and on the other hand will increase neuroactive kynurenines that may have a neurotoxic effect and increase inflammation. Considering its crucial physiological effects, melatonin deficiency has been linked to the development of neurological and psychological diseases, by letting the central nervous system unprotected from reactive species that will favor oxidative stress and neuroinflammation. This review will give new insights on the balance between the two tryptophan metabolic pathways and how they are associated with pathophysiological mechanisms. In addition, this work assesses the relevance of melatonin administration, or its precursor tryptophan, since they are relatively safe molecules, as potential therapeutic interventions of some neuropsychological diseases. The aim of this supplementation is to improve the quality of sleep, diminish the development and progression of the disease and relieve symptoms. However, it is important to adapt the dose for each individual, so further studies are needed in order to avoid empirical administration, improving safety and its rational use.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Triptofano Distúrbios do sono Doenças neuroinflamatórias Quinurenina Melatonina Mestrado integrado - 2020