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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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Marcuzzi A,Piscianz E,Zweyer M,Bortul R,Loganes C,Girardelli M,Baj G,Monasta L,Celeghini C

doi

10.3390/ijms17030365

subject

Has Abstract

pub_date

2016-03-11 00:00:00

pages

365

issue

3

issn

1422-0067

pii

ijms17030365

journal_volume

17

pub_type

杂志文章

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