N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase primarily found in the endosomal-lysosomal compartment of innate and adaptive immune cells. NAAA catalyzes the hydrolytic deactivation of palmitoylethanolamide (PEA), a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that exerts profound anti-inflammatory effects in animal models. Emerging evidence points to NAAA-regulated PEA signaling at PPAR-α as a critical control point for the induction and the resolution of inflammation and to NAAA itself as a target for anti-inflammatory medicines. The present Perspective discusses three key aspects of this hypothesis: the role of NAAA in controlling the signaling activity of PEA; the structural bases for NAAA function and inhibition by covalent and noncovalent agents; and finally, the potential value of NAAA-targeting drugs in the treatment of human inflammatory disorders.

N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition / Piomelli, D; Scalvini, L; Fotio, Y; Lodola, A; Spadoni, G; Tarzia, G; Mor, M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 63:14(2020), pp. 7475-7490. [10.1021/acs.jmedchem.0c00191]

N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition

Piomelli D;Scalvini L;Lodola A;Tarzia G;Mor M.
2020-01-01

Abstract

N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase primarily found in the endosomal-lysosomal compartment of innate and adaptive immune cells. NAAA catalyzes the hydrolytic deactivation of palmitoylethanolamide (PEA), a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that exerts profound anti-inflammatory effects in animal models. Emerging evidence points to NAAA-regulated PEA signaling at PPAR-α as a critical control point for the induction and the resolution of inflammation and to NAAA itself as a target for anti-inflammatory medicines. The present Perspective discusses three key aspects of this hypothesis: the role of NAAA in controlling the signaling activity of PEA; the structural bases for NAAA function and inhibition by covalent and noncovalent agents; and finally, the potential value of NAAA-targeting drugs in the treatment of human inflammatory disorders.
2020
N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition / Piomelli, D; Scalvini, L; Fotio, Y; Lodola, A; Spadoni, G; Tarzia, G; Mor, M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 63:14(2020), pp. 7475-7490. [10.1021/acs.jmedchem.0c00191]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2880149
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