@article {10440,
	title = {Neuronal Dysfunction Associated with Cholesterol Deregulation.},
	journal = {Int J Mol Sci},
	volume = {19},
	year = {2018},
	month = {2018 May 19},
	abstract = {<p>Cholesterol metabolism is crucial for cells and, in particular, its biosynthesis in the central nervous system occurs in situ, and its deregulation involves morphological changes that cause functional variations and trigger programmed cell death. The pathogenesis of rare diseases, such as Mevalonate Kinase Deficiency or Smith$^{-}$Lemli$^{-}$Opitz Syndrome, arises due to enzymatic defects in the cholesterol metabolic pathways, resulting in a shortage of downstream products. The most severe clinical manifestations of these diseases appear as neurological defects. Expanding the knowledge of this biological mechanism will be useful for identifying potential targets and preventing neuronal damage. Several studies have demonstrated that deregulation of the cholesterol pathway induces mitochondrial dysfunction as the result of respiratory chain damage. We set out to determine whether mitochondrial damage may be prevented by using protective mitochondria-targeted compounds, such as MitoQ, in a neuronal cell line treated with a statin to induce a biochemical block of the cholesterol pathway. Evidence from the literature suggests that mitochondria play a crucial role in the apoptotic mechanism secondary to blocking the cholesterol pathway. Our study shows that MitoQ, administered as a preventive agent, could counteract the cell damage induced by statins in the early stages, but its protective role fades over time.</p>},
	keywords = {Anticholesteremic Agents, Cell Line, Tumor, Cholesterol, Electron Transport, Humans, Lovastatin, Mitochondria, Neurons, Neuroprotective Agents, Organophosphorus Compounds, Ubiquinone},
	issn = {1422-0067},
	doi = {10.3390/ijms19051523},
	author = {Marcuzzi, Annalisa and Loganes, Claudia and Valencic, Erica and Piscianz, Elisa and Monasta, Lorenzo and Bilel, Sabrine and Bortul, Roberta and Celeghini, Claudio and Zweyer, Marina and Tommasini, Alberto}
}
@article {1674,
	title = {Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes.},
	journal = {Int Immunopharmacol},
	volume = {10},
	year = {2010},
	month = {2010 Jun},
	pages = {639-42},
	abstract = {<p>The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1beta release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates.</p>},
	keywords = {Animals, Cell Line, Cells, Cultured, Child, Child, Preschool, Cytokines, Diphosphonates, Humans, Inflammation, Interleukin-1beta, Lipopolysaccharides, Male, Mevalonate Kinase Deficiency, Mice, Monocytes, Nitric Oxide, Terpenes},
	issn = {1878-1705},
	doi = {10.1016/j.intimp.2010.03.008},
	author = {Marcuzzi, Annalisa and Tommasini, Alberto and Crovella, Sergio and Pontillo, Alessandra}
}
