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.

中文翻译：

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N-酰基乙醇胺酸酰胺酶（NAAA）：结构，功能和抑制作用。

ñ-酰基乙醇胺酸酰胺酶（NAAA）是N端半胱氨酸水解酶，主要存在于先天和适应性免疫细胞的内体-溶酶体区室。NAAA催化棕榈酰乙醇酰胺（PEA）的水解失活，这是一种脂质衍生的过氧化物酶体增殖物激活的受体-α（PPAR-α）激动剂，在动物模型中发挥着深远的消炎作用。越来越多的证据表明，PPAR-α上NAAA调控的PEA信号是诱导和解决炎症的关键控制点，而NAAA本身则是抗炎药物的靶标。本观点讨论了这一假设的三个关键方面：NAAA在控制PEA信号传导活性中的作用；NAAA功能和被共价和非共价试剂抑制的结构基础；最后，