Acetylcholinesterase and Nicotinic Acetylcholine Receptors in Schistosomes and Other Parasitic Helminths

Abstract

Schistosomiasis, which is caused by helminth trematode blood flukes of the genus Schistosoma, is a serious health and economic problem in tropical areas, and the second most prevalent parasitic disease after malaria. Currently, there is no effective vaccine available and treatment is entirely dependent on a single drug, praziquantel (PZQ), raising a significant potential public health threat due to the emergence of PZQ drug resistance. It is thus urgent and necessary to explore novel therapeutic targets for the treatment of schistosomiasis. Previous studies demonstrated that acetylcholinesterase (AChE) and nicotinic acetylcholine receptors (nAChRs) play important roles in the schistosome nervous system and ion channels, both of which are targeted by a number of currently approved and marketed anthelminthic drugs. To improve understanding of the functions of the cholinergic system in schistosomes, this article reviews previous studies on AChE and nAChRs in schistosomes and other helminths and discusses their potential as suitable targets for vaccine development and drug design against schistosomiasis.

Insects in anthelminthics research: Lady beetle-derived harmonine affects survival, reproduction and stem cell proliferation of Schistosoma mansoni

“…AChE is a well-characterized enzyme, also in schistosomes, and it is the presumed target of metrifonate, a formerly used antischistosomal drug [35]. AChE was found to be abundantly expressed in the tegument of schistosomes [36, 37]. Therefore, we hypothesized that AChE might be one target of harmonine in S .…”

“…haematobium , S . japonicum , and S. bovis , AChE fulfills two different functions: a classical role in the neuromuscular system for motor activity, and a non-classical role in the tegument related to glucose import from host blood [37, 55]. The tegumental damage observed in harmonine-treated worms might be correlated with the high tegumental expression of AChE [38, 56, 57], while the observed paralysis might be linked to the neuromuscular role.…”

Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes

“…Further research might validate AChE as a possible vaccine target. AChE was also detected in other helminths besides schistosomes, such as in N. brasiliensis, Fasciola hepatica, and Dipylidium caninum (34).…”

CRISPR/Cas9: A new tool for the study and control of helminth parasites

“…Acetylcholinesterase is a recognized anthelminthic target, playing key roles in the adult schistosome neuromusculature cholinergic system, and in muscular function. [85] Recently, You et al [48] undertook CRISPR/Cas9 editing of S. mansoni eggs targeting the gene (AChE) encoding acetylcholinesterase. Eggs were transfected by electroporation with reconstructed CRISPR/Cas9-plasmidsencoding specific sgR-NAs driven by the U6 promoter and Cas9 nuclease driven by the CMV promoter.…”

“…Acetylcholinesterase is a recognized anthelminthic target, playing key roles in the adult schistosome neuromusculature cholinergic system, and in muscular function. [ 85 ] Recently, You et al. [ 48 ] undertook CRISPR/Cas9 editing of S. mansoni eggs targeting the gene ( AChE ) encoding acetylcholinesterase.…”