Delay of neurodegenerative disease by Nano-PSO (GranaGard) is associated with restoring normal
mitochondrial function

Neurodegenerative diseases are associated with the accumulation of specific
misfolded proteins, and with severe oxidative damage, leading to mitochondrial
malfunction. Previous work in our lab has shown that long term administration of
GranaGard, a brain targeted antioxidant composed of a nanodroplet formulation of
pomegranate seed oil (PSO) to Tg mice modeling for genetic prion disease,
significantly delayed disease advance and neuronal death. To elucidate the
mechanism of action of GranaGard, we compared brain mitochondrial enzyme
activity and ROS/ATP production at different ages of the model mice. Concomitantly,
we looked in parallel brain samples for the expression of mitochondrial enzymes and
oxidation response factors. We found that while brain mitochondrial respiratory chain
enzymatic activates and ATP/ROS production, were abnormally elevated in
asymptomatic mice and then reduced in old and sick Tg mice, the same parameters in
the samples of treated Tg brains were similar to those of wt mice. Similar results were
obtained when brain slices were immunostained for Cytochrome c oxidase (COX)
subunit IV isoform 1(Cox IV-1) as compared to Cox IV isoform 2, an isoform that
operates in oxidative neuronal conditions. Our results indicate that brain targeted
antioxidants such as GranaGard can correct mitochondrial function in
neurodegenerative conditions.