N-acylethanolamine-hydrolyzing acid amidase (NAAA)

N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal N-terminal cysteine hydrolase of the choloylglycine hydrolase family, structurally and functionally akin to acid ceramidase. It preferentially hydrolyzes saturated and monounsaturated N-acylethanolamines such as palmitoylethanolamide (PEA), a bioactive lipid with established anti-inflammatory and analgesic properties, rapidly degrading them into fatty acids and ethanolamine primarily at acidic pH. NAAA expression is highest in macrophage-rich tissues (e.g., lung, spleen, thymus). Its activity attenuates pro-resolving lipid signaling, particularly the actions of PEA on peroxisome proliferator-activated receptor-α (PPAR-α), and is a key factor in the regulation of inflammation, pain, and possibly neuroinflammatory diseases. Pharmacological inhibition of NAAA results in increased tissue levels of PEA and other N-acylethanolamines, amplifying their analgesic and anti-inflammatory effects—and is therefore under active investigation as a drug target for chronic pain, inflammation, and neurological disease.

Other names

ASAH-like proteinASAHLN-palmitoylethanolamine acid amidaseAcid ceramidase-like protein

Inhibition of NAAA leads to increased endogenous N-acylethanolamines (e.g., palmitoylethanolamide), resulting in enhanced anti-inflammatory and analgesic signaling (primarily via PPAR-α activation); inhibition decreases hydrolysis and inactivation of these lipid mediators