Nematode nicotinic acetylcholine receptor like-23 (ACR-23)

The **nematode nicotinic acetylcholine receptor like-23 (ACR-23)** is a homopentameric ligand-gated cation channel found in nematodes, most studied in *Caenorhabditis elegans*[1][5]. It belongs to the Cys-loop family of ligand-gated ion channels and is structurally homologous to mammalian α7 nicotinic acetylcholine receptors, although it is nematode-specific and has significant differences in ligand specificity[1][3]. ACR-23 functions primarily as a betaine-gated channel with key roles in maintaining normal locomotion in nematodes[3]. The anthelmintic drug monepantel, from the amino-acetonitrile derivative (AAD) class, exerts its effects by acting as a positive allosteric modulator of ACR-23, causing prolonged activation, hypercontraction of body wall muscles, and death of the worm[1][3][5]. Loss-of-function mutations in acr-23 confer resistance to monepantel, making it a major marker for drug efficacy and resistance surveillance[5]. ACR-23 is a validated therapeutic target for nematode control and is highly selective for nematode channels, minimizing safety concerns for use in agriculture and veterinary medicine[1][5].

Other names

ACR-23acetylcholine receptor like-23betaine receptor (context-dependent)monepantel receptor (context-dependent)

Positive allosteric modulation (monepantel induces channel opening); Agonist activation (betaine acts as endogenous agonist; monepantel acts as modulator and indirect agonist); Overactivation leads to hypercontraction and nematode paralysis and death