title: Liver X receptors activation, through TO901317 binding, reduces neuroinflammation in Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disease in which degeneration of nigrostriatal neurons and inflammation are key players. The aim of our study was to analyze the function of LXRs in neurodegenerative diseases as PD using in vivo, ex vivo and in vitro models of PD; for this purpose, we observed the effects of the LXR agonist, TO901317, in neuroinflammatory pathway related to PD. We performed an in vivo model of PD using the neurotoxin 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) and our results clearly showed that TO901317 administration reduces all of the inflammatory markers involved in PD such as iNOS and COX2, IκB-α and NF-κB. Moreover, to confirm the neuroprotective properties of TO901317, that we obtained with the in vivo model, we performed also an ex vivo and in vitro models of PD. All the results taken, confirmed that TO901317 is able to modulate the neuroinflammatory pathway involved in PD increasing the locomotors function. Therefore, TO901317, LXR synthetic agonist, could be studied as a new target in a neurodegenerative disorder like PD.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.|Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Salvatore
authors.identifier: http://orcid.org/0000-0001-6131-3690
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism* / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D000071518:Liver X Receptors / Q000819:agonists*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013449:Sulfonamides / Q000378:metabolism* / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D051546:Cyclooxygenase 2; D050483:Dopamine Plasma Membrane Transport Proteins; D006845:Hydrocarbons, Fluorinated; D018836:Inflammation Mediators; D000071518:Liver X Receptors; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; D013449:Sulfonamides; D014446:Tyrosine 3-Monooxygenase; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse