Acetylcholine receptor subunit acr-23 (ACR-23) (ACR-23)

Acetylcholine receptor subunit acr-23 (ACR-23), also known as Monepantel-sensitive receptor 1 (MPTL-1), is a critical component of a nematode-specific nicotinic acetylcholine receptor (nAChR) (Kaminsky et al., 2008, Nature). It belongs to the DEG-3 subfamily of ligand-gated ion channels, which are phylogenetically distinct from the nAChRs found in vertebrate hosts (Rufener et al., 2009, Molecular and Biochemical Parasitology). This receptor is primarily expressed in the nervous system and muscles of nematodes, where it facilitates neuromuscular transmission and coordinates locomotion (UniProt P49158). ACR-23 is the definitive molecular target for the amino-acetonitrile derivative (AAD) class of anthelmintics, specifically monepantel (Baur et al., 2015, PLOS Pathogens). When monepantel binds to the receptor, it acts as a potent agonist, causing the channel to remain open and leading to an exhaustive influx of cations (Rufener et al., 2010, PLoS Neglected Tropical Diseases). This overstimulation results in rapid muscle hypercontraction, spastic paralysis, and the eventual death of the parasite. Because the DEG-3 subfamily is absent in mammals, ACR-23 provides a high margin of safety and selectivity for treating helminth infections in livestock (Lecová et al., 2014, Parasitology Research). However, the emergence of resistance, often characterized by loss-of-function mutations or deletions in the acr-23 gene, remains a significant challenge in veterinary medicine.

Other names

MPTL-1Monepantel-sensitive receptor 1DEG-3 subfamily nicotinic acetylcholine receptor subunitacr-23

Agonist of the nematode-specific DEG-3 subfamily nicotinic acetylcholine receptor, causing persistent channel opening, depolarization, and spastic paralysis (Kaminsky et al., 2008).