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Int. J. Mol. Sci. 2016, 17(7), 1028;

TSPO PIGA Ligands Promote Neurosteroidogenesis and Human Astrocyte Well-Being

Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy
Author to whom correspondence should be addressed.
Academic Editor: Giovanni Natile
Received: 11 May 2016 / Revised: 22 June 2016 / Accepted: 23 June 2016 / Published: 29 June 2016
(This article belongs to the Special Issue Translocator Protein (TSPO))
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The steroidogenic 18 kDa translocator protein (TSPO) is an emerging, attractive therapeutic tool for several pathological conditions of the nervous system. Here, 13 high affinity TSPO ligands belonging to our previously described N,N-dialkyl-2-phenylindol-3-ylglyoxylamide (PIGA) class were evaluated for their potential ability to affect the cellular Oxidative Metabolism Activity/Proliferation index, which is used as a measure of astrocyte well-being. The most active PIGA ligands were also assessed for steroidogenic activity in terms of pregnenolone production, and the values were related to the metabolic index in rat and human models. The results showed a positive correlation between the increase in the Oxidative Metabolism Activity/Proliferation index and the pharmacologically induced stimulation of steroidogenesis. The specific involvement of steroid molecules in mediating the metabolic effects of the PIGA ligands was demonstrated using aminoglutethimide, a specific inhibitor of the first step of steroid biosynthesis. The most promising steroidogenic PIGA ligands were the 2-naphthyl derivatives that showed a long residence time to the target, in agreement with our previous data. In conclusion, TSPO ligand-induced neurosteroidogenesis was involved in astrocyte well-being. View Full-Text
Keywords: translocator protein; neurosteroidogenesis; PIGA ligands; cellular proliferation; oxidative metabolism; astrocytes translocator protein; neurosteroidogenesis; PIGA ligands; cellular proliferation; oxidative metabolism; astrocytes

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Da Pozzo, E.; Giacomelli, C.; Costa, B.; Cavallini, C.; Taliani, S.; Barresi, E.; Da Settimo, F.; Martini, C. TSPO PIGA Ligands Promote Neurosteroidogenesis and Human Astrocyte Well-Being. Int. J. Mol. Sci. 2016, 17, 1028.

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