Details

Autor(en) / Beteiligte

• Bottemanne, Pauline
• Muccioli, Giulio G.
• Alhouayek, Mireille

Titel

N-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential therapeutic opportunities

Ist Teil von

• Drug discovery today, 2018-08, Vol.23 (8), p.1520-1529

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• •NAAA is a key enzyme controlling the levels of bioactive N-acylethanolamines.•Novel, systemically active inhibitors are now available to study NAAA roles in vivo.•NAAA inhibition appears beneficial in conditions related to inflammation and pain. N-acylethanolamines (NAEs) (e.g., N-palmitoylethanolamine, N-arachidonoylethanolamine, N-oleoylethanolamine) are bioactive lipids involved in many physiological processes including pain, inflammation, anxiety, cognition and food intake. Two enzymes are responsible for the hydrolysis of NAEs and therefore regulate their endogenous levels and effects: fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA). As discussed here, extensive biochemical characterization of NAAA was carried out over the years that contributed to a better understanding of NAAA enzymology. An increasing number of studies describe the synthesis and pharmacological characterization of NAAA inhibitors. Recent medicinal chemistry efforts have led to the development of potent and stable inhibitors that enable studying the effects of NAAA inhibition in preclinical disease models, notably in the context of pain and inflammation.