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Melatonin has significant neuroprotective properties, which have been related to its ability to boost mitochondrial bioenergetics. The meaning and molecular targets of melatonin in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> are yet unclear. Zebrafish are an outstanding model of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> because they are vertebrates, their dopaminergic system is comparable to the nigrostriatal system of humans, and their brains express the same genes as mammals. The exposure of 24 hpf zebrafish embryos to <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> leads to a significant inhibition of the mitochondrial complex I and the induction of <jats:italic>sncga<\/jats:italic> gene, responsible for enhancing <jats:italic>\u03b3<\/jats:italic>\u2010synuclein accumulation, which is related to mitochondrial dysfunction. Moreover, <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> inhibited the <jats:italic>parkin\/<jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>1<\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">DJ<\/jats:styled-content>\u20101<\/jats:italic> expression, impeding the normal function of the parkin\/<jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">DJ<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">MUL<\/jats:styled-content>1 network to remove the damaged mitochondria. This situation remains over time, and removing <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> from the treatment did not stop the neurodegenerative process. On the contrary, mitochondria become worse during the next 2 days without <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>, and the embryos developed a severe motor impairment that cannot be rescued because the mitochondrial\u2010related gene expression remained inhibited. Melatonin, added together with <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> or added once <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content> was removed, prevented and recovered, respectively, the parkinsonian phenotype once it was established, restoring gene expression and normal function of the parkin\/<jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">DJ<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">MUL<\/jats:styled-content>1 loop and also the normal motor activity of the embryos. 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