Deregulation of the mevalonate pathway is known to be involved in a number of
diseases that exhibit a systemic inflammatory phenotype and often neurological
involvements, as seen in patients suffering from a rare disease called mevalonate kinase
deficiency (MKD). One of the molecular mechanisms underlying this pathology could
depend on the shortage of isoprenoid compounds and the subsequent mitochondrial
damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover,
it has been demonstrated that cellular death results from the balance between apoptosis
and pyroptosis, both driven by mitochondrial damage and the molecular platform
inflammasome. In order to rescue the deregulated pathway and decrease inflammatory
markers, exogenous isoprenoid compounds were administered to a biochemical model of
MKD obtained treating a murine monocytic cell line with a compound able to block the
mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids
acted in different ways, mainly increasing the expression of the evaluated markers
[apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like
receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the
hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids.
