Can cholinesterase inhibitors affect neural development?

Accumulating evidence supports the view that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) can influence the proliferation and differentiation of nerve cells. AChE in particular has been found to promote neurite outgrowth in a variety of model systems, possibly by serving as an adhesion molecule. Thus one might suspect that cholinesterase inhibitors would disturb neuronal development, with long-term implications for structure and function in the central and peripheral nervous systems. The actual picture is more complex because AChE's effects on neurite outgrowth may reflect protein-protein interactions that are not directly related to catalytic function but are nonetheless influenced by ligands with special structural features. The putative structural interactions have not yet been rigorously defined, but they are likely to involve enzyme regions at or near the peripheral anionic site. In addition to such effects, some organophosphorus anticholinesterases have been reported to act by still other mechanisms to depress macromolecule synthesis and cell survival in the developing brain. Taken together, this emerging information highlights the potential importance of anticholinesterase agents in developmental neurotoxicology.