title: Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology.
abstract: Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. annalisa.marcuzzi@burlo.trieste.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marcuzzi
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. elisa.piscianz@gmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscianz
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. zweyer@units.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Zweyer
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. bortul@univ.trieste.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bortul
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. claudia.loganes@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Loganes
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. martina.girardelli@burlo.trieste.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Girardelli
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. gbaj@units.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. lorenzo.monasta@burlo.trieste.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monasta
authors.affiliation: Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. cceleghini@units.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Celeghini
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D054078:Mevalonate Kinase Deficiency / Q000378:metabolism* / Q000473:pathology; D008798:Mevalonic Acid / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D004224:Diterpenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C017338:geranylgeraniol; D008798:Mevalonic Acid
keywords: apoptosis; cholesterol pathway; mevalonate; mitochondria; neuroinflammation; neuronal death