title: Synergetic Neuroprotective Effect of Docosahexaenoic Acid and Aspirin in SH-Y5Y by Inhibiting miR-21 and Activating RXRα and PPARα.
abstract: Parkinson's disease (PD) is a serious neurodegenerative disorder that lacks effective therapeutic methods. In this research, expressions of PPARα, RXRα, and miR-21 were evaluated in PD patients and normal controls. To investigate the effects of miR-21, docosahexaenoic acid (DHA) and aspirin (ASA) on PD, as well as the relationships between them, SH-Y5Y cells were treated with DHA, ASA, or both for 24 h. The assay showed that levels of miR-21 were increased and levels of PPARα were decreased in PD patients compared with normal controls. miR-21 was negatively correlated with PPARα in PD patients. DHA and ASA could activate RXRα and PPARα, respectively. Additionally, DHA upregulated PPARα expression by inhibiting miR-21 in SH-Y5Y cells. A combination of DHA and ASA efficiently enhanced heterodimer formations of PPARα and RXRα and increased the expression of neurotrophic factors PSD-95, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), while inhibiting NFκB and COX2. These findings suggest that a combination of DHA and ASA could significantly improve the expression of PSD-95, BDNF, and GDNF by promoting heterodimerization of PPARα and RXRα, thus supplying a new therapeutic method for PD.
authors.affiliation: 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University , Wuhan, China .
authors.forename: Yongwang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 2 Department of Neurology, Inner Mongolia Autonomous Region People's Hospital , Hohhot, China .
authors.forename: Jin
authors.initials: J
authors.lastname: Zhen
authors.affiliation: 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University , Wuhan, China .
authors.forename: Zuneng
authors.initials: Z
authors.lastname: Lu
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; D047493:PPAR alpha; D047490:Retinoid X Receptor alpha; D004281:Docosahexaenoic Acids; D001241:Aspirin
keywords: ASA; DHA; PPARα; Parkinson's disease; RXRα; miR-21