Open AccessLiver X receptors activation, through TO901317 binding, reduces neuroinflammation in Parkinson’s disease
Author(s) -
Irene Paterniti,
Michela Campolo,
Rosalba Siracusa,
Marika Cordaro,
Rosanna Di Paola,
Vittorio Calabrese,
Michele Navarra,
Salvatore Cuzzocrea,
Emanuela Esposito
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0174470
Subject(s) - agonist , mptp , neuroprotection , neuroinflammation , parkinson's disease , in vivo , neurotoxin , ex vivo , pharmacology , neuroscience , receptor , medicine , biology , chemistry , inflammation , disease , microbiology and biotechnology
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.