Neurosteroids: biochemistry and clinical significance
@article{Mellon2002NeurosteroidsBA,
title={Neurosteroids: biochemistry and clinical significance},
author={Synthia H. Mellon and Lisa D. Griffin},
journal={Trends in Endocrinology \& Metabolism},
year={2002},
volume={13},
pages={35-43},
url={https://api.semanticscholar.org/CorpusID:11605131}
}511 Citations
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How local synthesis and metabolism of neurosteroids are modulated in the central nervous system are reviewed and described and whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders is discussed.
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Steroidogenesis in the nervous system is regulated by interactions between neurons and glial cells, and drugs that affect synthesis or metabolism of neurosteroids provide a new therapeutic opportunity for treatment of these disorders.
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It has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin production by the pineal gland and eye inhibits the biosynthesis of 7α-hydroxypregnenolone, while prolactin produced by the adenohypophysis enhances the formation of 7 α-OH-Δ5P.
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The biosynthetic pathways and the expression of enzymes and receptors of progesterone; as well as the changes observed after brain injuries and in neurological diseases; and the key role of the classical progester one receptors (PR) in mediating the neuroprotective effects of progestersone after stroke are highlighted.
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The hypothesis that differences between males and females in local neurosteroid production may contribute to sex differences in the development of neurodegenerative disease is explored.
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The paired association between rehabilitation and neurosteroids treatment could provide a boosting effect in order to promote neuroplasticity and therefore functional recovery in neurological patients.
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Medicine, Biology
This paper summarizes what is known about the biosynthesis of neurosteroids, the enzymes mediating these reactions, their localization during development and in the adult, and their function and mechanisms of action in the developing and adult central and peripheral nervous systems.
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It is demonstrated that P450c17 is expressed in the nervous system of the developing rodent embryo, suggesting it is a marker for the axonal growth in this region, and that its neurosteroid product may be a signal for targeting cortical axons during embryogenesis.
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