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Organophosphate pesticides affect mammalian brain development through mechanisms separable from the inhibition of acetylcholinesterase (AChE) enzymatic activity and resultant cholinergic hyperstimulation. In the brain, AChE has two catalytically similar splice variants with distinct functions in development and repair. The rare, read-through isoform, AChE-R, is preferentially induced by injury and appears to promote repair and protect against neurodegeneration. Overexpression of the more abundant, synaptic isoform, AChE-S, enhances neurotoxicity.

environmental health perspectives

Nonenzymatic Functions of Acetylcholinesterase Splice Variants in the Developmental Neurotoxicity of Organophosphates: Chlorpyrifos, Chlorpyrifos Oxon, and Diazinon