2. Academic Validation
  3. Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

  • Int J Mol Sci. 2016 Mar 11;17(3):365. doi: 10.3390/ijms17030365.
Annalisa Marcuzzi 1,  Elisa Piscianz 2,  Marina Zweyer 3,  Roberta Bortul 4,  Claudia Loganes 5,  Martina Girardelli 6,  Gabriele Baj 7,  Lorenzo Monasta 8,  Claudio Celeghini 9
Affiliations

Affiliations

  • 1 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. annalisa.marcuzzi@burlo.trieste.it.
  • 2 Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. elisa.piscianz@gmail.com.
  • 3 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. zweyer@units.it.
  • 4 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. bortul@univ.trieste.it.
  • 5 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. claudia.loganes@gmail.com.
  • 6 Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. martina.girardelli@burlo.trieste.it.
  • 7 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. gbaj@units.it.
  • 8 Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, Trieste 34137, Italy. lorenzo.monasta@burlo.trieste.it.
  • 9 Piazzale Europa 1, University of Trieste, Trieste 34127, Italy. cceleghini@units.it.
PMID: 26978350 DOI: 10.3390/ijms17030365
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.

Keywords

apoptosis; cholesterol pathway; mevalonate; mitochondria; neuroinflammation; neuronal death.

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