Investigation of a novel mechanism of cholinergic activation for cognitive impairment treatment

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Cholinergic neurons are involved in cognitive function in the central nervous system. At the cholinergic presynaptic terminals, acetylcholine synthesis relies on the high-affinity choline transporter (CHT1) for efficient choline supply from extracellular fluid. The choline uptake is the rate-limiting step in acetylcholine synthesis. We find that extracellular substrate regulates the cell surface CHT1 by enhancing its internalization rate. We also find that tetrahydropyrimidines are competitive inhibitors of CHT1.