title: The Association of Palmitoylethanolamide with Luteolin Decreases Neuroinflammation and Stimulates Autophagy in Parkinson's Disease Model.
abstract: 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.
authors: Rosalba
authors: R
authors: Siracusa
authors: Irene
authors: I
authors: Paterniti
authors: Daniela
authors: D
authors: Impellizzeri
authors: Marika
authors: M
authors: Cordaro
authors: Rosalia
authors: R
authors: Crupi
authors: Michele
authors: M
authors: Navarra
authors: Salvatore
authors: S
authors: Cuzzocrea
authors: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31 - 98166 Messina, Italy. eesposito@unime.it.
authors: Emanuela
authors: E
authors: Esposito
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D004983:Ethanolamines; D018696:Neuroprotective Agents; C000610984:co-ultraPEALut; D047311:Luteolin