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OBJECTIVE DL0410,one novel compound discovered inhigh throughput screening(HTS),was found to be a potent inhibitor for AChE and BuChE.Memory deficit mice model induced by scopolamine have been conducted to verify its effects on the improvement of memory deficit.In this study,the effects of DL0410 on inhibitingβ-amyloid(Aβ)aggregation and attenuating cognition and memory impairment of APP/PS1 mice were further investigated.METHODS Th-T binding test was used to determinethe effect of DL0410 on Aβ1-42 aggregation.In addition,locomotor test,object recognition test,step-down test,and Morris Water maze were performedto investigate the effect of DL0410 on the cognition and memoryfunctions of APP/PS1 mice.RESULTS In vitro results showed that DL0410(10and 30μmol·L-1)could inhibit significantly the monomer Aβ1-42 from aggregation,when incubated together with monomer Aβ1-42 for 24h(P<0.01).Several behavioral tests demonstrated that DL0410(10and 30mg·kg-1)could shortened latency time innavigation test(P<0.01),increased platform crossing-times in space probe test(P<0.05),and reduced the error times in step-down test(P<0.01).CONCLUSIONDL0410 could inhibit Aβaggregation in vitro and alleviate cognition and memory impairment of APP/PS1 mice,which make DL0410 apromising candidate for Alzheimer′s disease treatment.
OBJECTIVE DL0410, one novel compound discovered in high throughput screening (HTS), was found to be potent inhibitor for AChE and BuChE. Memory deficit mice model induced by scopolamine have been administered to verify its effects on the improvement of memory deficit. In this study , the effects of DL0410 on inhibitingβ-amyloid (Aβ) aggregation and attenuating cognition and memory impairment of APP / PS1 mice were further investigated. METHODS Th-T binding test was used to determine the effect of DL0410 on Aβ1-42 aggregation.In addition, locomotor test, object recognition test, step-down test, and Morris Water maze were performed to investigate the effect of DL0410 on the cognition and memory activities of APP / PS1 mice. RESULTS In vitro results showed that DL0410 (10 and 30 μmol·L-1) could inhibit significantly the monomer Aβ1-42 from aggregation, when incubated together with monomer Aβ1-42 for 24h (P <0.01). Prevenural behavioral tests demonstrated that DL0410 (10 and 30 mg · kg -1) could shortened latency time innav (P <0.01) .CONCLUSIONDL0410 could inhibit Aβaggregation in vitro and alleviate cognition and memory impairment of APP / PS1 mice, which make DL0410 apromising candidate for Alzheimer’s disease treatment.