Parkinson's disease (PD) is a disorder resulted by degeneration of dopaminergic neurons.
To counteract the neuroinflammation and oxidative stress of PD, we decided to test a new composite
constituted by palmitoylethanolamide (PEA) and luteolin (Lut), in a mass ratio of 10:1, respectively
(co-ultraPEALut). In this study the neuroprotective property of the new compound was investigated.
For the in vivo model of PD, mice received four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP). Starting 24 h after the first administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP), we treated animals with co-ultraPEALut daily until 7 days. On day 8, brains were processed for Western blotting
and immunohistochemical analysis. Treatment with co-ultraPEALut reduced the specific markers of PD (tyrosine
hydroxylase immunopositive), and the increased levels of activated astrocytes and pro-inflammatory cytokines as well as
inducible nitric oxide synthase. Further, the possible association of autophagy with the beneficial effects of coultraPEALut.
Western blot analysis and immunofluorescence staining showed that co-ultraPEALut administration
increased autophagy process. These data were confirmed by an in vitro model, using SH-SY5Y neuroblastoma cells.
Western blot analysis showed that co-ultraPEALut pre-treatment maintained high Beclin-1 and p62 expression, while
continued to inhibit the p70S6K expression. Altogether, these results put forward that treatment with co-ultraPEALut is
able to modulate both the neuroinflammatory process and the autophagic pathway involved in PD, actions which may
underlie its neuroprotective effect.