| First Author | Patel D | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 31 | Pages | E7408-E7417 |
| PubMed ID | 30012602 | Mgi Jnum | J:267741 |
| Mgi Id | MGI:6193987 | Doi | 10.1073/pnas.1802021115 |
| Citation | Patel D, et al. (2018) Aspirin binds to PPARalpha to stimulate hippocampal plasticity and protect memory. Proc Natl Acad Sci U S A 115(31):E7408-E7417 |
| abstractText | Despite its long history, until now, no receptor has been identified for aspirin, one of the most widely used medicines worldwide. Here we report that peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear hormone receptor involved in fatty acid metabolism, serves as a receptor of aspirin. Detailed proteomic analyses including cheminformatics, thermal shift assays, and TR-FRET revealed that aspirin, but not other structural homologs, acts as a PPARalpha ligand through direct binding at the Tyr314 residue of the PPARalpha ligand-binding domain. On binding to PPARalpha, aspirin stimulated hippocampal plasticity via transcriptional activation of cAMP response element-binding protein (CREB). Finally, hippocampus-dependent behavioral analyses, calcium influx assays in hippocampal slices and quantification of dendritic spines demonstrated that low-dose aspirin treatment improved hippocampal plasticity and memory in FAD5X mice, but not in FAD5X/Ppara-null mice. These findings highlight a property of aspirin: stimulating hippocampal plasticity via direct interaction with PPARalpha. |
