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.

The Relation of the Brain-Derived Neurotrophic Factor with MicroRNAs in Neurodegenerative Diseases and Ischemic Stroke

“…Importantly, the study showed that DHA increased neurotrophic factors such as GDNF and BDNF. Thus, authors hypothesized that DHA upregulates PPARα expression by miR-21 inhibitor and activates RXRα, which reveals induced BDNF, functioned as a neuroprotective factor [60].…”

Untargeted Metabolomics to Go beyond the Canonical Effect of Acetylsalicylic Acid

“…We assume that an increase of methylglutarylcarnitine reflects increased peroxisomal oxidation, such a metabolite having been suggested as a marker of this process [50]. ASA is known to induce peroxisome proliferator-activated receptor alpha expression and activity [51], thus boosting β-oxidation. Moreover, ASA-AMPK activation switches off ATP-consuming processes, while switching on catabolic pathways that generate ATP, a major event in the fatty acid oxidation process [52].…”

Нестероидные Противовоспалительные Средства: Ключевые Механизмы Действия И Нейропротективный Потенциал

“… èññëåäîâàíèè [25] îöåíèâàëè ýêñïðåññèþ PPAR-a, ÿäåðíîãî ðåöåïòîðà RXRa, è ìèêðîÐÍÊ miR-21 ó ïàöèåíòîâ ñ ÁÏ ïî ñðàâíåíèþ ñ êîíòðîëüíîé ãðóïïîé. Óñòàíîâëåíî, ÷òî ñî÷åòàíèå äîêîçàãåêñàåíîâîé êèñëîòû (DHA) è ÀÑÊ ñìîãëî çíà÷èòåëüíî óëó÷øèòü ýêñïðåññèþ áåëêà PSD-95, íåéðîòðîôè÷åñêèõ ôàêòîðîâ BDNF è GDNF ïðè ïîâûøåíèè ãåòåðîäèìå-ðèçàöèè PPAR-a è RXRa, ÷òî ìîaeåò ÿâëÿòüñÿ íîâûì ïîäõîäîì ê ëå÷åíèþ ÁÏ.…”