Molecular Neurobiology

, Volume 55, Issue 12, pp 9251–9266 | Cite as

2-Pentadecyl-2-Oxazoline Reduces Neuroinflammatory Environment in the MPTP Model of Parkinson Disease

  • Marika Cordaro
  • Rosalba Siracusa
  • Rosalia Crupi
  • Daniela Impellizzeri
  • Alessio Filippo Peritore
  • Ramona D’Amico
  • Enrico Gugliandolo
  • Rosanna Di Paola
  • Salvatore Cuzzocrea


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 signaling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal cell degeneration of the dopaminergic tract induced by four intraperitoneal injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on 8-week-old male C57 mice. Moreover, PEA-OXA treatment 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 upregulation 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. In conclusion, pharmacological activation of nuclear factor E2-related factor 2 pathways with PEA-OXA may be effective in the future therapy of PD.


2-Pentadecyl-2-oxazoline Inflammation Nrf-2 Parkinson disease 



The authors would like to thank Maria Antonietta Medici for the excellent technical assistance during this study, Mr. Francesco Soraci for the secretarial and administrative assistance, and Miss Valentina Malvagni for the editorial assistance with the manuscript.

Compliance with Ethical Standards

Conflict of Interest

Dr. Salvatore Cuzzocrea is co-inventor on patent WO2013121449A8 (Epitech Group SpA) which deals with compositions and methods for the modulation of amidases capable of hydrolysing N-acylethanolamines applied in the therapy of inflammatory diseases. Moreover, Dr. Cuzzocrea is also a co-inventor with the Epitech group on the following patents:

1. EP2821,083

2. MI2014A001495

3. 102015000067344

None of the other authors have any conflicts of interest to declare.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Marika Cordaro
    • 1
  • Rosalba Siracusa
    • 1
  • Rosalia Crupi
    • 1
  • Daniela Impellizzeri
    • 1
  • Alessio Filippo Peritore
    • 1
  • Ramona D’Amico
    • 1
  • Enrico Gugliandolo
    • 1
  • Rosanna Di Paola
    • 1
  • Salvatore Cuzzocrea
    • 1
    • 2
  1. 1.Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
  2. 2.Department of Pharmacological and Physiological ScienceSaint Louis University School of MedicineSt LouisUSA

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