| First Author | Chiozzi P | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 6475 |
| PubMed ID | 31019207 | Mgi Jnum | J:279846 |
| Mgi Id | MGI:6357466 | Doi | 10.1038/s41598-019-42931-2 |
| Citation | Chiozzi P, et al. (2019) Amyloid beta-dependent mitochondrial toxicity in mouse microglia requires P2X7 receptor expression and is prevented by nimodipine. Sci Rep 9(1):6475 |
| abstractText | Previous data from our laboratory show that expression of the P2X7 receptor (P2X7R) is needed for amyloid beta (Abeta)-stimulated microglia activation and IL-1beta release in vitro and in vivo. We also showed that Abeta-dependent stimulation is inhibited by the dihydropyridine nimodipine at an intracellular site distal to the P2X7R. In the present study, we used the N13 microglia cell line and mouse primary microglia from wt and P2rx7-deleted mice to test the effect of nimodipine on amyloid beta (Abeta)-dependent NLRP3 inflammasome expression and function, and on mitochondrial energy metabolism. Our data show that in microglia Abeta causes P2X7R-dependent a) NFkappaB activation; b) NLRP3 inflammasome expression and function; c) mitochondria toxicity; and these changes are fully inhibited by nimodipine. Our study shows that nimodipine is a powerful blocker of cell damage caused by monomeric and oligomeric Abeta, points to the mitochondria as a crucial target, and underlines the permissive role of the P2X7R. |
