Cholinesterases (ChEs) and the cholinergic system in ontogenesis and phylogenesis, and non-classical roles of cholinesterases—A review

The enigma of the cholinergic function concerns the role of ChEs and other components of the cholinergic system in non-transmittive, non-synaptic phenomena. The notion that such unorthodox, non-classical phenomena must exist is clearly supported by several lines of evidence, such as the presence of ChEs and other cholinergic components early before neurogenesis, and indeed in unfertilized and fertilized eggs and in the sperm of many species, and their presence throughout phylogenesis, including non-motile, monocellular organisms, fungi and plants and many anervous and ephemeral tissues. The “flexibility” of ChEs, expressed in their polymorphism and their changeability during ontogenesis also speaks for the notion of non-classical functions of ChEs. Today, there is direct evidence that such functions do indeed exist, as for example, the evidence as to the role of ChEs and other cholinergic components in processes of cell proliferation and differentiation of synaptic and myoneural structures. Also, ChEs participate in cell communications as examplified by immunity processes, as well as pathological states, including Alzheimer's disease and states induced by “insults” such as stress and exposure to agents such as antiChEs. Finally, consistent with the non-classical roles of ChEs and cholinergic components are the morphogenetic and teratologic effects of antiChEs, including OP compounds and cholinergic agonists and antagonists. The structural homology between ChEs on the one hand, and adhesion molecules and protohormones on the other may explain some of this phenomenology. It is proposed that the phylogenetic ubiquity of ChEs and their basic capacities that are important for evolutionary phylogenesis, such as the capacity to promote cell adhesion and cell communication speaks for ChEs as “Ur” proteins.