TY - JOUR T1 - Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology. JF - Int J Mol Sci Y1 - 2016 A1 - Marcuzzi, Annalisa A1 - Piscianz, Elisa A1 - Zweyer, Marina A1 - Bortul, Roberta A1 - Loganes, Claudia A1 - Girardelli, Martina A1 - Baj, Gabriele A1 - Monasta, Lorenzo A1 - Celeghini, Claudio AB -

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.

VL - 17 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26978350?dopt=Abstract ER -