Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-42931-2
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Funding
- Italian Association for Cancer Research [IG 13025, IG 18581, IG 16812]
- Ministry of Education of Italy [PRIN 20178YTNWC]
- Ministry of Health of Italy [RF-2011-02348435]
- University of Ferrara
- European H2020 office through the COST Action Ion channels and Immune response [BM1406]
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Previous data from our laboratory show that expression of the P2X7 receptor (P2X7R) is needed for amyloid beta(A beta)-stimulated microglia activation and IL-1 beta release in vitro and in vivo. We also showed that A beta-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(A beta)-dependent NLRP3 inflammasome expression and function, and on mitochondrial energy metabolism. Our data show that in microglia A beta causes P2X7R-dependent a) NF kappa B 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 A beta, points to the mitochondria as a crucial target, and underlines the permissive role of the P2X7R.
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