Inhibition of Muscle-Specific Protein Kinase (MuSK) Releases Organophosphate-Aged Acetylcholinesterase (AChE) from C2C12 Cells.

Monica Moncada-Restrepo¹, Sarah Eysoldt², Jeronimo Medina³, Valentina Di Guida⁴, Jeremy W Chambers¹

¹Department of Biology & Microbiology, College of Natural Sciences, South Dakota State University, Brookings, SD 57007, USA.

²Proscia, Inc., Philadelphia, PA 19103, USA.

³Department of Environmental Health Sciences, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL 33199, USA.

⁴Department of Biological Sciences, College of Arts, Sciences, and Education, Florida International University, Miami, FL 33199, USA.

PubMed PMC DOI PDF

Abstract

Mechanistically, OPs inhibit acetylcholinesterase (AChE), an enzyme that terminates cholinergic transmission, triggering a sustained activation of acetylcholine receptors. A component of the treatment for OP intoxication is oximes as AChE reactivators. However, oximes may not be efficacious and could worsen OP effects. Further, dealkylation of the AChE-OP adducts prevents oxime reactivation. There…

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