PMID- 28346830 OWN - NLM STAT- MEDLINE DCOM- 20170908 LR - 20170908 IS - 1557-7430 (Electronic) IS - 1044-5498 (Linking) VI - 36 IP - 6 DP - 2017 Jun TI - Synergetic Neuroprotective Effect of Docosahexaenoic Acid and Aspirin in SH-Y5Y by Inhibiting miR-21 and Activating RXRalpha and PPARalpha. PG - 482-489 LID - 10.1089/dna.2017.3643 [doi] AB - Parkinson's disease (PD) is a serious neurodegenerative disorder that lacks effective therapeutic methods. In this research, expressions of PPARalpha, RXRalpha, 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 PPARalpha were decreased in PD patients compared with normal controls. miR-21 was negatively correlated with PPARalpha in PD patients. DHA and ASA could activate RXRalpha and PPARalpha, respectively. Additionally, DHA upregulated PPARalpha expression by inhibiting miR-21 in SH-Y5Y cells. A combination of DHA and ASA efficiently enhanced heterodimer formations of PPARalpha and RXRalpha and increased the expression of neurotrophic factors PSD-95, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), while inhibiting NFkappaB 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 PPARalpha and RXRalpha, thus supplying a new therapeutic method for PD. FAU - Fu, Yongwang AU - Fu Y AD - 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University , Wuhan, China . FAU - Zhen, Jin AU - Zhen J AD - 2 Department of Neurology, Inner Mongolia Autonomous Region People's Hospital , Hohhot, China . FAU - Lu, Zuneng AU - Lu Z AD - 1 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University , Wuhan, China . LA - eng PT - Journal Article DEP - 20170327 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (MIRN21 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Neuroprotective Agents) RN - 0 (PPAR alpha) RN - 0 (Retinoid X Receptor alpha) RN - 25167-62-8 (Docosahexaenoic Acids) RN - R16CO5Y76E (Aspirin) SB - IM MH - Aspirin/*pharmacology MH - Base Sequence MH - Cell Line, Tumor MH - Docosahexaenoic Acids/*pharmacology MH - Drug Synergism MH - Humans MH - MicroRNAs/*antagonists & inhibitors MH - Neuroprotective Agents/*pharmacology MH - PPAR alpha/agonists/genetics/*metabolism MH - Retinoid X Receptor alpha/agonists/*metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - ASA OT - DHA OT - PPARalpha OT - Parkinson's disease OT - RXRalpha OT - miR-21 EDAT- 2017/03/28 06:00 MHDA- 2017/09/09 06:00 CRDT- 2017/03/28 06:00 PHST- 2017/03/28 06:00 [pubmed] PHST- 2017/09/09 06:00 [medline] PHST- 2017/03/28 06:00 [entrez] AID - 10.1089/dna.2017.3643 [doi] PST - ppublish SO - DNA Cell Biol. 2017 Jun;36(6):482-489. doi: 10.1089/dna.2017.3643. Epub 2017 Mar 27.