I conducted experiments in Drosophila to investigate the consequences of altered acetylcholinesterase (AChE) activity in the nervous system. In ace hypomorphic mutant larvae, the amount of ace mRNA and the activity of AChE both in vivo and in vitro were significantly reduced compared with those of controls. Reduced Ace in Drosophila larvae resulted in significant down-regulation of branch length and the number of boutons in Type 1 glutamatergic neuromuscular junctions (NMJs). These defects in ace hypomorphic mutant larvae were suppressed when Musca domestica AChE was transgenically expressed. Because AChE inhibitors are utilized for medications for Alzheimer’s disease, we investigated whether pharmacological inhibition of AChE activity induced any synaptic defects. I found that controls exposed to a sublethal dose of DDVP phenocopied the synaptic structural defects of the ace hypomorphic mutant. These results suggest that down-regulation of AChE activity, regardless of whether it is due to genetic or pharmacological manipulations, results in altered synaptic architecture. This study suggests that exposure to AChE inhibitors for 6-12 months may induce altered synaptic architectures in human brains with Alzheimer’s diseases, similar to those reported here. These changes may underlie or contribute to the loss of efficacy of AChE inhibitors after prolonged treatment.

The acetylcholinesterase (AChE) inhibition of 12 plant-derived insecticidal compounds (anethol, anisaldehyde, 3-carene, 1,8-cineol, ethyl-cinnamate, linalool, magnolol, ethyl-p-methoxycinnamate, p-methoxycinamic acid, safrol, terpinen-4-ol, and α-terpineol) towards adult mosquitoes were examined by using Ellman method. Result were compared with those of dichlorvos, a potent AChE inhibitor. 3-Carene strongly inhibited AChE (IC50, 5.78×10-4 M), although the inhibition of the compound was lower than dichlorvos (IC50, 1.45×10-4 M). These results indicate that 3-carene acts as an AChE inhibitor, although an involvement of other insecticidal mechanism(s) might not be ruled out.

Background : This study was conducted to select candidates from among plant resources with the potential to improve Alzheimer’s disease (AD), the most common form of dementia. AD has been linked to a deficiency in the brain neurotransmitter acetylcholine (ACh), and is also correlated with cholinergic system abnormalities coupled with progressive cognitive impairment and altered behavior. The activity of ACh in the brain is terminated by the hydrolysis action of cholinesterase (ChEs). An inhibitor of these enzymes could contribute to improving the level of ACh and to augmenting the activity of surviving cholinergic neurons in patients with AD. Methods and Results : Plant extracts were prepared by solvent extraction and tested for acetylcholinesterase (AChE) inhibitory activity by using the Ellman colorimetric method. One hundred and eighty-four extracts at a final concentration of 100 ㎍/㎖ were preliminarily screened for their AChE inhibition capacity. From the experiment, the AChE inhibitory activity of five extracts including a methanol extract of Coptis chinensis (rhizome), a methanol extract of Nelumbo nucifera Gaertn (stamen/ovary), a methanol extract of Persicaria tinctoria H.GROSS (flower), and both a methanol extract and a water extract of Phellaodendron amurense Rupr (bark) showed comparatively higher AChE inhibitory effects, ranging from 38.3 to 63.1%, than other extracts. The five selected extracts were retested for their AChE inhibition activity at final concentrations of 25, 50, 100, and 200 ㎍/㎖, and compared with tacrine (0.1 ㎍/㎖) as the positive control. In the experiment, the five extracts effectively inhibited AChE at each of the set concentrations. Conclusion : The results of this study indicate that the five plant extracts mentioned above could be utilized as candidates for improving the ACh level and for ameliorating AD.