Synergetic Neuroprotective Effect of Docosahexaenoic Acid and Aspirin in SH-Y5Y by Inhibiting miR-21 and Activating RXRα and PPARα.

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.