Geranylgeraniol and neurological impairment

Involvement of apoptosis and mitochondrial morphology

Annalisa Marcuzzi, Elisa Piscianz, Marina Zweyer, Roberta Bortul, Claudia Loganes, Martina Girardelli, Gabriele Baj, Lorenzo Monasta, Claudio Celeghini

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number365
JournalInternational Journal of Molecular Sciences
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 11 2016

Fingerprint

Mevalonic Acid
Mitochondria
mitochondria
impairment
apoptosis
Cell death
Deregulation
Apoptosis
markers
mevalonate kinase
damage
pathogenesis
Mevalonate Kinase Deficiency
Cell Death
Oxidative stress
Cholesterol
cholesterol
Inflammasomes
cultured cells
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Keywords

  • Apoptosis
  • Cholesterol pathway
  • Mevalonate
  • Mitochondria
  • Neuroinflammation
  • Neuronal death

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

Cite this

Geranylgeraniol and neurological impairment : Involvement of apoptosis and mitochondrial morphology. / Marcuzzi, Annalisa; Piscianz, Elisa; Zweyer, Marina; Bortul, Roberta; Loganes, Claudia; Girardelli, Martina; Baj, Gabriele; Monasta, Lorenzo; Celeghini, Claudio.

In: International Journal of Molecular Sciences, Vol. 17, No. 3, 365, 11.03.2016.

Research output: Contribution to journalArticle

Marcuzzi, Annalisa ; Piscianz, Elisa ; Zweyer, Marina ; Bortul, Roberta ; Loganes, Claudia ; Girardelli, Martina ; Baj, Gabriele ; Monasta, Lorenzo ; Celeghini, Claudio. / Geranylgeraniol and neurological impairment : Involvement of apoptosis and mitochondrial morphology. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 3.
@article{4ccf313e55104ea6b96c8563b64b9e7f,
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.",
keywords = "Apoptosis, Cholesterol pathway, Mevalonate, Mitochondria, Neuroinflammation, Neuronal death",
author = "Annalisa Marcuzzi and Elisa Piscianz and Marina Zweyer and Roberta Bortul and Claudia Loganes and Martina Girardelli and Gabriele Baj and Lorenzo Monasta and Claudio Celeghini",
year = "2016",
month = "3",
day = "11",
doi = "10.3390/ijms17030365",
language = "English",
volume = "17",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "3",

}

TY - JOUR

T1 - Geranylgeraniol and neurological impairment

T2 - Involvement of apoptosis and mitochondrial morphology

AU - Marcuzzi, Annalisa

AU - Piscianz, Elisa

AU - Zweyer, Marina

AU - Bortul, Roberta

AU - Loganes, Claudia

AU - Girardelli, Martina

AU - Baj, Gabriele

AU - Monasta, Lorenzo

AU - Celeghini, Claudio

PY - 2016/3/11

Y1 - 2016/3/11

N2 - 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.

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.

KW - Apoptosis

KW - Cholesterol pathway

KW - Mevalonate

KW - Mitochondria

KW - Neuroinflammation

KW - Neuronal death

UR - http://www.scopus.com/inward/record.url?scp=84961247479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961247479&partnerID=8YFLogxK

U2 - 10.3390/ijms17030365

DO - 10.3390/ijms17030365

M3 - Article

VL - 17

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 3

M1 - 365

ER -