2-Pentadecyl-2-Oxazoline reduces neuroinflammatory environment in the MPTP model of Parkinson Disease

Abstract Background and Aim: Current pharmacological management of Parkinson disease (PD) does not provide for disease modification, but addresses only symptomatic features. Here, we explore a new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA-OXA), the oxazoline derivative of the fatty acid amide signalling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Methods: Eight-week-old male C57 mice received four intraperitoneal injections of 20mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in saline at 2-h intervals in 1 day, the entire dose per mouse being 80 mg/kg. PEA-OXA (10 mg/kg) was orally administered starting 24 h after the first MPTP injection and continuing through 7 additional days after the last injection of MPTP. Results: Daily orally treatment with PEA-OXA significantly prevented dopamine depletion, increased tyrosine hydroxylase and dopamine transporter activities and decreased α-synuclein aggregation in neurons. PEA-OXA treatment also diminished nuclear factor-κB traslocation, cyclooxygenase-2 and inducible nitric oxide synthase expression and through up-regulation of the nuclear factor E2-related factor 2 pathway, induced activation of Mn-superoxide dismutase and heme oxygenase-1. Further, PEA-OXA modulated microglia and astrocyte activation, and preserved microtubule associated protein-2 alterations. Conclusion: In summary, our results clearly demonstrate the several beneficial functions of PEA-OXA treatment. In fact, this compound is able to improve neurobehavioral functions, the integrity of the neuronal tissue with consequent reduction of the cell death, and to modulate the neuroinflammatory pathway involved in PD. Thus, our observations indicate that PEA-OXA may be considered as a new therapeutic target to improve neurodegenerative disorders such as PD..