Schistosoma mansoni acetylcholinesterase (SmAChE)

Schistosoma mansoni acetylcholinesterase (SmAChE) is a vital enzyme in the parasitic blood fluke Schistosoma mansoni, where it catalyzes the hydrolysis of the neurotransmitter acetylcholine to terminate cholinergic signaling (Bueding, 1952; NIH, 2025). The enzyme exists in two distinct functional forms encoded by separate genes: a neuronal form (SmAChE1) primarily associated with the parasite's internal musculature and a tegumental form (SmTAChE or SmAChE3) anchored to the external surface (Frontiers in Immunology, 2019; MDPI, 2025). While the neuronal form is essential for motor activity and coordination, the tegumental form is uniquely involved in non-neuronal processes, including the regulation of host-parasite interactions and the facilitation of glucose uptake from the host's blood (ResearchGate, 2025). SmAChE has long been targeted for the treatment of schistosomiasis, most notably by the organophosphate drug metrifonate, which is metabolized into the active inhibitor dichlorvos (WHO, 2017). However, the clinical use of such inhibitors is limited by their potential to cross-react with human acetylcholinesterase, leading to host toxicity and cholinergic side effects (PubMed, 2017). Modern therapeutic strategies aim to exploit the structural differences between the parasite and human enzymes to develop highly selective inhibitors that can paralyze and eliminate the worms without harming the host (NIH, 2025).

Other names

SmAChESmTAChESmAChE1SmAChE3Schistosome acetylcholinesterase

Inhibition of acetylcholinesterase activity leads to the accumulation of acetylcholine at cholinergic synapses and the parasite surface, resulting in neuromuscular paralysis, impaired glucose scavenging, and eventual death of the parasite.