title: The Association of Palmitoylethanolamide with Luteolin Decreases Autophagy in Spinal Cord Injury.
abstract: Spinal cord injury (SCI) is a devastating condition of the central nervous system (CNS) often resulting in severe functional impairment and for which there are not yet restorative therapies. In the present study, we performed a widely used model of SCI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound co-ultraPEALut. In particular, by western blot analysis and immunofluorescence staining, we investigated whether this compound (at the dose of 1 mg/kg) was able to modulate autophagy. Our results showed that treatment with co-ultraPEALut after SCI reduced the expression of proteins promoter of autophagy such as Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (MAP-LC3). In contrast, this compound decreased the levels of mammalian target of rapamycin (mTOR), p-Akt, and p-70S6K which are proteins that inhibit autophagy. These data confirmed that the protective role of co-ultraPEALut is associated with inhibition of excessive autophagy and regulation of protein degradation. Therefore, treatment with co-ultraPEALut could be considered as a possible therapeutic approach in an acute traumatic lesion like SCI.
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy.|Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St Louis, MO, 63104, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, 98166, Messina, Italy. eesposito@unime.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000577:Amides; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010169:Palmitic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000071456:Sequestosome-1 Protein / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000577:Amides; D000071186:Beclin-1; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D004983:Ethanolamines; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D010169:Palmitic Acids; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C000610984:co-ultraPEALut; C005958:palmidrol; D047311:Luteolin
keywords: Anti-inflammatory; Anti-oxidant; Autophagy; Neuroprotection; Spinal compression