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Liver X receptors activation decreases neuroinflammation in Parkinson’s disease (846.5)
Author(s) -
Campolo Michela,
Paterniti Irene,
Siracusa Rosalba,
Bruschetta Giuseppe,
Cuzzocrea Salvatore,
Esposito Emanuela
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.846.5
Subject(s) - agonist , mptp , neuroinflammation , liver x receptor , substantia nigra , dopaminergic , in vivo , receptor , chemistry , pharmacology , parkinson's disease , biology , dopamine , neuroscience , inflammation , microbiology and biotechnology , medicine , nuclear receptor , immunology , biochemistry , disease , transcription factor , gene
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic nigrostriatal neurons, progressive loss of substantia nigra and inflammation. Liver X receptors (LXRs) are considered as potent anti‐inflammatory molecules in macrophages and neuronal cells. The aim of this study was to investigate the role of LXRs in neurodegenerative disorders like PD using in vivo, in vitro and ex vivo models; for this purpose, we studied the effect of the synthetic LXR agonist, TO901317, in neuroinflammatory pathway related to PD. Our results showed a reduction in neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced cell death, iNOS and COX2 expression, IκB‐α degradation, and NF‐κB translocation after treatment with TO901317. Moreover, in in vitro study, through SH‐SY5Y cells, we demonstrated an important restoration of neuthrophic factors (GDNF) and nNOS expression. Moreover, in in vivo study, mice exhibited a significantly recovery of motor function after TO901317 treatment. In the light of the results obtained, TO901317, a synthetic LXR agonist, is able to modulate the neuroinflammatory pathway involved in PD increasing the locomotors function. Therefore, LXRs could be considered as a possible therapeutic target in a neurodegenerative disorders like PD.