Figure 10.

Schematic diagram of the underlying mechanism of cholinergic function modulation by GSK‐3 activation. (A) ChAT is synthesized in the cell body of cholinergic neurons and transported to the synaptic terminals along the microtubules and neurofilaments for catalyzing the biosynthesis of ACh. GSK‐3 was activated via dephosphorylation at Ser9 epitope or overexpression in our present study; then, the microtubules and neurofilaments were hyperphosphorylated (B), which resulted in microtubule stability decline and neurofilaments aggregation (C). Both morphological abnormity prevented the smooth ChAT transport and led to the swelling formation in the axons, which correspondingly decreased the ChAT concentration in the neurite terminals and down‐regulated the ACh level ultimately (C). Activated GSK‐3 phosphorylated NF‐κB/p100 and promoted its cleavage into p52. The active p52 migrated into the nucleus and inhibited mRNA level of ChAT (C and D). Our experiments directly illustrated the underlying mechanism about regulatory relationship between GSK‐3 and ChAT.