Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization

International Journal of Molecular Sciences

卷:22

Maddalena Grieco¹  Maria D’Erme¹  Mauro Maccarrone²  Patrizia Mancini³  Maria Giovanna De Caris³  Federica Armeli⁴  Rita Businaro⁴  Elisa Maggi⁴  Tiziana Bisogno⁵  Roberto Coccurello⁶ 

[1] Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;

[2] Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio snc, 67100 L’Aquila, Italy;

[3] Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy;

[4] Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy;

[5] Endocannabinoid Research Group, Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy;

[6] Fondazione Santa Lucia IRCCS, Preclinical Neuroscience, Via del Fosso di Fiorano 64, 00143 Rome, Italy;

关键词: URB597;    N-arachidonoylethanolamine (AEA);    fatty acid amide hydrolase (FAAH);    microglia;    actin cytoskeleton;    cell migration;   

DOI  :  10.3390/ijms22147711

来源: DOAJ

【 摘 要 】

The ability of endocannabinoid (eCB) to change functional microglial phenotype can be explored as a possible target for therapeutic intervention. Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer’s disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-β peptide (Aβ). The morphological evaluation showed that Aβ treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology. URB597 treatment partially rescued the control phenotype of BV-2 cells when co-incubated with Aβ. Moreover, URB597 reduced both the increase of Rho protein activation in Aβ-treated BV-2 cells and the Aβ-induced migration of BV-2 cells, while an increase of Cdc42 protein activation was observed in all samples. URB597 also increased the number of BV-2 cells involved in phagocytosis. URB597 treatment induced the polarization of microglial cells towards an anti-inflammatory phenotype, as demonstrated by the decreased expression of iNOS and pro-inflammatory cytokines along with the parallel increase of Arg-1 and anti-inflammatory cytokines. Taken together, these data suggest that FAAH inhibition promotes cytoskeleton reorganization, regulates phagocytosis and cell migration processes, thus driving microglial polarization towards an anti-inflammatory phenotype.

【 授权许可】

Unknown