N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibition, but Not Fatty Acid Amide Hydrolase Inhibition, Prevents the Development of Experimental Autoimmune Encephalomyelitis in Mice.
Demyelination
Lipid mediator
N-acyltaurine
N-palmitoylethanolamine
Neuroinflammation
PEA
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
accepted:
13
06
2021
pubmed:
9
7
2021
medline:
4
3
2022
entrez:
8
7
2021
Statut:
ppublish
Résumé
N-acylethanolamines (NAEs) are endogenous bioactive lipids reported to exert anti-inflammatory and neuroprotective effects mediated by cannabinoid receptors and peroxisome proliferator-activated receptors (PPARs), among others. Therefore, interfering with NAE signaling could be a promising strategy to decrease inflammation in neurological disorders such as multiple sclerosis (MS). Fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA) are key modulators of NAE levels. This study aims to investigate and compare the effect of NAAA inhibition, FAAH inhibition, and dual inhibition of both enzymes in a mouse model of MS, namely the experimental autoimmune encephalomyelitis (EAE). Our data show that NAAA inhibition strongly decreased the hallmarks of the pathology. Interestingly, FAAH inhibition was less efficient in decreasing inflammatory hallmarks despite the increased NAE levels. Moreover, the inhibition of both NAAA and FAAH, using a dual-inhibitor or the co-administration of NAAA and FAAH inhibitors, did not show an added value compared to NAAA inhibition. Furthermore, our data suggest an important role of decreased activation of astrocytes and microglia in the effects of NAAA inhibition on EAE, while NAAA inhibition did not affect T cell recall. This work highlights the beneficial effects of NAAA inhibition in the context of central nervous system inflammation and suggests that the simultaneous inhibition of NAAA and FAAH has no additional beneficial effect in EAE.
Identifiants
pubmed: 34235639
doi: 10.1007/s13311-021-01074-x
pii: 10.1007/s13311-021-01074-x
pmc: PMC8609003
doi:
Substances chimiques
Enzyme Inhibitors
0
PF 3845
0
Piperidines
0
Pyridines
0
Amidohydrolases
EC 3.5.-
NAAA protein, mouse
EC 3.5.1.-
fatty-acid amide hydrolase
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1815-1833Informations de copyright
© 2021. The American Society for Experimental NeuroTherapeutics, Inc.
Références
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-58.
pubmed: 26250739
Li C, Wu X, Liu S, Shen D, Zhu J, Liu K. Role of Resolvins in the Inflammatory Resolution of Neurological Diseases. Front Pharmacol. 2020;11:612.
pubmed: 32457616
pmcid: 7225325
Ernest James Phillips T, Maguire E. Phosphoinositides: Roles in the Development of Microglial-Mediated Neuroinflammation and Neurodegeneration. Front Cell Neurosci. 2021;15:652593.
Alhouayek M, Ameraoui H, Muccioli GG. Bioactive lipids in inflammatory bowel diseases - From pathophysiological alterations to therapeutic opportunities. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866(2):158854.
Tao X, Lee MS, Donnelly CR, Ji RR. Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain. Neurotherapeutics. 2020;17(3):886-99.
pubmed: 32696274
pmcid: 7609770
Portavella M, Rodriguez-Espinosa N, Galeano P, Blanco E, Romero JI, Holubiec MI, et al. Oleoylethanolamide and Palmitoylethanolamide Protect Cultured Cortical Neurons Against Hypoxia. Cannabis Cannabinoid Res. 2018;3(1):171-8.
pubmed: 30255158
pmcid: 6148719
Scuderi C, Stecca C, Valenza M, Ratano P, Bronzuoli MR, Bartoli S, et al. Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer’s disease. Cell Death Dis. 2014;5:e1419.
Schurman LD, Lichtman AH. Endocannabinoids: A Promising Impact for Traumatic Brain Injury. Front Pharmacol. 2017;8:69.
pubmed: 28261100
pmcid: 5314139
Petrosino S, Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br J Pharmacol. 2017;174(11):1349-65.
pubmed: 27539936
Hernangomez M, Mestre L, Correa FG, Loria F, Mecha M, Inigo PM, et al. CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation. Glia. 2012;60(9):1437-50.
pubmed: 22653796
Gonzalez-Aparicio R, Blanco E, Serrano A, Pavon FJ, Parsons LH, Maldonado R, et al. The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. Int J Neuropsychopharmacol. 2014;17(3):455-68.
pubmed: 24169105
Beggiato S, Tomasini MC, Ferraro L. Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease. Front Pharmacol. 2019;10:821.
pubmed: 31396087
pmcid: 6667638
Siracusa R, Paterniti I, Impellizzeri D, Cordaro M, Crupi R, Navarra M, et al. The Association of Palmitoylethanolamide with Luteolin Decreases Neuroinflammation and Stimulates Autophagy in Parkinson's Disease Model. CNS Neurol Disord Drug Targets. 2015;14(10):1350-65.
pubmed: 26295827
Esposito E, Impellizzeri D, Mazzon E, Paterniti I, Cuzzocrea S. Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson’s disease. PLoS One. 2012;7(8):e41880.
Rahimi A, Faizi M, Talebi F, Noorbakhsh F, Kahrizi F, Naderi N. Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice. Neuroscience. 2015;290:279-87.
pubmed: 25637488
Loria F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangomez M, et al. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci. 2008;28(4):633-41.
pubmed: 18657182
Orefice NS, Alhouayek M, Carotenuto A, Montella S, Barbato F, Comelli A, et al. Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-beta1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis. Neurotherapeutics. 2016;13(2):428-38.
pubmed: 26857391
pmcid: 4824021
Ueda N, Tsuboi K, Uyama T. Metabolism of endocannabinoids and related N-acylethanolamines: canonical and alternative pathways. FEBS J. 2013;280(9):1874-94.
pubmed: 23425575
Muccioli GG. Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today. 2010;15(11-12):474-83.
pubmed: 20304091
Bottemanne P, Muccioli GG, Alhouayek M. N-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential therapeutic opportunities. Drug Discov Today. 2018;23(8):1520-9.
pubmed: 29567427
Piomelli D, Scalvini L, Fotio Y, Lodola A, Spadoni G, Tarzia G, et al. N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition. J Med Chem. 2020.
Webb M, Luo L, Ma JY, Tham CS. Genetic deletion of Fatty Acid Amide Hydrolase results in improved long-term outcome in chronic autoimmune encephalitis. Neurosci Lett. 2008;439(1):106-10.
pubmed: 18501510
Rossi S, Furlan R, De Chiara V, Muzio L, Musella A, Motta C, et al. Cannabinoid CB1 receptors regulate neuronal TNF-alpha effects in experimental autoimmune encephalomyelitis. Brain Behav Immun. 2011;25(6):1242-8.
pubmed: 21473912
Pryce G, Cabranes A, Fernandez-Ruiz J, Bisogno T, Di Marzo V, Long JZ, et al. Control of experimental spasticity by targeting the degradation of endocannabinoids using selective fatty acid amide hydrolase inhibitors. Mult Scler. 2013;19(14):1896-904.
pubmed: 23625705
Migliore M, Pontis S, Fuentes de Arriba AL, Realini N, Torrente E, Armirotti A, et al. Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis. Angew Chem Int Ed Engl. 2016;55(37):11193–7.
Malamas MS, Farah SI, Lamani M, Pelekoudas DN, Perry NT, Rajarshi G, et al. Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors. Bioorg Med Chem. 2020;28(1):115195.
Sagheddu C, Scherma M, Congiu M, Fadda P, Carta G, Banni S, et al. Inhibition of N-acylethanolamine acid amidase reduces nicotine-induced dopamine activation and reward. Neuropharmacology. 2019;144:327-36.
pubmed: 30439418
Orefice NS, Guillemot-Legris O, Capasso R, Bottemanne P, Hantraye P, Caraglia M, et al. miRNA profile is altered in a modified EAE mouse model of multiple sclerosis featuring cortical lesions. Elife. 2020;9.
Alhouayek M, Bottemanne P, Subramanian KV, Lambert DM, Makriyannis A, Cani PD, et al. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. FASEB J. 2015;29(2):650-61.
pubmed: 25384424
Guillemot-Legris O, Masquelier J, Everard A, Cani PD, Alhouayek M, Muccioli GG. High-fat diet feeding differentially affects the development of inflammation in the central nervous system. J Neuroinflammation. 2016;13(1):206.
pubmed: 27566530
pmcid: 5002131
Mutemberezi V, Buisseret B, Masquelier J, Guillemot-Legris O, Alhouayek M, Muccioli GG. Oxysterol levels and metabolism in the course of neuroinflammation: insights from in vitro and in vivo models. J Neuroinflammation. 2018;15(1):74.
pubmed: 29523207
pmcid: 5845224
Alhouayek M, Bottemanne P, Makriyannis A, Muccioli GG. N-acylethanolamine-hydrolyzing acid amidase and fatty acid amide hydrolase inhibition differentially affect N-acylethanolamine levels and macrophage activation. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(5):474-84.
pubmed: 28065729
De Berdt P, Bottemanne P, Bianco J, Alhouayek M, Diogenes A, Lloyd A, et al. Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion. Cell Mol Life Sci. 2018;75(15):2843-56.
pubmed: 29417177
Mutemberezi V, Masquelier J, Guillemot-Legris O, Muccioli GG. Development and validation of an HPLC-MS method for the simultaneous quantification of key oxysterols, endocannabinoids, and ceramides: variations in metabolic syndrome. Anal Bioanal Chem. 2016;408(3):733-45.
pubmed: 26563111
Contarini G, Giusti P, Skaper SD. Active Induction of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice. Methods Mol Biol. 2018;1727:353-60.
pubmed: 29222794
Aharoni R, Globerman R, Eilam R, Brenner O, Arnon R. Titration of myelin oligodendrocyte glycoprotein (MOG) - Induced experimental autoimmune encephalomyelitis (EAE) model. J Neurosci Methods. 2021;351:108999.
Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16(1):9-29.
pubmed: 31831863
Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov. 2018;17(9):623-39.
pubmed: 30116049
Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, et al. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol. 2009;16(4):411-20.
pubmed: 19389627
pmcid: 2692831
Lassmann H. Pathology of inflammatory diseases of the nervous system: Human disease versus animal models. Glia. 2020;68(4):830-44.
pubmed: 31605512
Frezel N, Sohet F, Daneman R, Basbaum AI, Braz JM. Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE. Exp Neurol. 2016;283(Pt A):224-34.
pubmed: 27343802
pmcid: 5500277
Gobel K, Ruck T, Meuth SG. Cytokine signaling in multiple sclerosis: Lost in translation. Mult Scler. 2018;24(4):432-9.
pubmed: 29512406
Zilkha-Falb R, Rachutin-Zalogin T, Cleaver L, Gurevich M, Achiron A. RAM-589.555 favors neuroprotective and anti-inflammatory profile of CNS-resident glial cells in acute relapse EAE affected mice. J Neuroinflammation. 2020;17(1):313.
Griffin P, Dimitry JM, Sheehan PW, Lananna BV, Guo C, Robinette ML, et al. Circadian clock protein Rev-erbalpha regulates neuroinflammation. Proc Natl Acad Sci U S A. 2019;116(11):5102-7.
pubmed: 30792350
pmcid: 6421453
Tintore M, Vidal-Jordana A, Sastre-Garriga J. Treatment of multiple sclerosis - success from bench to bedside. Nat Rev Neurol. 2019;15(1):53-8.
pubmed: 30315270
Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010;162(1):1-11.
pubmed: 20682002
pmcid: 2990924
Long JZ, LaCava M, Jin X, Cravatt BF. An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase. J Lipid Res. 2011;52(2):337-44.
pubmed: 21097653
pmcid: 3023554
Bradshaw HB, Rimmerman N, Hu SS, Benton VM, Stuart JM, Masuda K, et al. The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathways. BMC Biochem. 2009;10:14.
pubmed: 19460156
pmcid: 2689249
Leishman E, Cornett B, Spork K, Straiker A, Mackie K, Bradshaw HB. Broad impact of deleting endogenous cannabinoid hydrolyzing enzymes and the CB1 cannabinoid receptor on the endogenous cannabinoid-related lipidome in eight regions of the mouse brain. Pharmacol Res. 2016;110:159-72.
pubmed: 27109320
pmcid: 4914450
Sasso O, Pontis S, Armirotti A, Cardinali G, Kovacs D, Migliore M, et al. Endogenous N-acyl taurines regulate skin wound healing. Proc Natl Acad Sci U S A. 2016;113(30):E4397-406.
pubmed: 27412859
pmcid: 4968764
Saghatelian A, McKinney MK, Bandell M, Patapoutian A, Cravatt BF. A FAAH-regulated class of N-acyl taurines that activates TRP ion channels. Biochemistry. 2006;45(30):9007-15.
pubmed: 16866345
Correa F, Hernangomez-Herrero M, Mestre L, Loria F, Docagne F, Guaza C. The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells. Brain Behav Immun. 2011;25(4):736-49.
pubmed: 21310228
Li Y, Zhou P, Chen H, Chen Q, Kuang X, Lu C, et al. Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid amidase (NAAA) inhibitor F215. Pharmacol Res. 2018;132:7-14.
pubmed: 29572189
Tsuboi K, Uyama T, Okamoto Y, Ueda N. Endocannabinoids and related N-acylethanolamines: biological activities and metabolism. Inflamm Regen. 2018;38:28.
pubmed: 30288203
pmcid: 6166290
Kong WL, Peng YY, Peng BW. Modulation of neuroinflammation: Role and therapeutic potential of TRPV1 in the neuro-immune axis. Brain Behav Immun. 2017;64:354-66.
pubmed: 28342781
Paltser G, Liu XJ, Yantha J, Winer S, Tsui H, Wu P, et al. TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. Mol Med. 2013;19:149-59.
pubmed: 23689362
pmcid: 3745593
Stampanoni BM, Gentile A, Iezzi E, Zagaglia S, Musella A, Simonelli I, et al. Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis. Front Neurol. 2019;10:30.
Wang Z, Zhou L, An D, Xu W, Wu C, Sha S, et al. TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice. Cell Death Dis. 2019;10(6):386.
pubmed: 31097691
pmcid: 6522539
Liu M, Liu X, Wang L, Wang Y, Dong F, Wu J, et al. TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci. 2018;12:392.
pubmed: 30455633
pmcid: 6230558
Jakaria M, Azam S, Haque ME, Jo SH, Uddin MS, Kim IS, et al. Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019;24:101223.
Beyer BA, Fang M, Sadrian B, Montenegro-Burke JR, Plaisted WC, Kok BPC, et al. Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation. Nat Chem Biol. 2018;14(1):22-8.
pubmed: 29131145