Dis-demethoxycurcumin Can Clear Aβ By Up-regulating SCARA1 And Improve Learning And Memory Ability In AD Mice

[Research background and purpose] Alzheimer’s disease is the main cause of Alzheimer’s disease.Its clinical manifestations of memory impairment and cognitive dysfunction have a great impact on the life of patients.The pathogenesis of β-amyloid(Aβ)waterfall is widely used.It is recognized that Aβ production and clearance imbalance are the initial events leading to neuronal degeneration and dementia.Therefore,it is particularly important to explore the mechanism of Aβ clearance and play an important role in the prevention and treatment of Alzheimer’s disease.The A1 scavenger receptor(SCARA1),as one of the receptors for the clearance of Aβ by immune cells,plays an important role in the progression of the disease.Studies have shown that curcumin can inhibit the formation of Aβ and play a neuroprotective role,and whether its mechanism is related to the expression of SCARA1 is not clear.Therefore,this study aimed to investigate the specific intrinsic mechanism of bis-demethoxycurcumin(BDMC)against Alzheimer’s disease(AD)and to determine whether BDMC can up-regulate SCARA1.Increase the clearance of Aβ in AD mice and improve their learning and memory ability to achieve the effect of antagonizing Alzheimer’s disease.[Methods] The first part explores the differences in the expression of SCARA1 in normal mice,APP/PS1 double transgenic mice and BDMC-interrogated APP/PS1 double transgenic mice:The experimental mice were divided into three groups: normal group(WT mouse),AD group(APP/PS1 double transgenosis mouse),and AD+BDMC group(BDMC intervention APP/PS1 double transgenosis mouse).The learning and memory function of each group of mice was observed by Morris water maze test and Y maze test.The deposition of Aβ in hippocampus of each mouse was detected by Aβ immunofluorescence staining.The expression of SCARA1 in hippocampus of each mouse was detected by Western blot.The second part explores whether the role of BDMC in the treatment of Alzheimer’s disease is related to the up-regulation of SCARA1expression: Firstly,the expression levels of SCARA1 in hippocampus of AD group(APP/PS1 double transgenosis mouse)and AD+Fucoidan group(Fucoidan intervention APP/PS1 double transgenic mice)were detected by Western blotting,to verify whether Fucoidan effectively inhibits the expression of SCARA1.The experimental mice were then divided into three groups:AD group(APP/PS1 double transgenosis mouse),AD+BDMC group(BDMC intervention APP/PS1 double transgenic mouse),and AD+Fuicoidan+BDMC group(Fucoidan and BDMC intervention APP/PS1 mouse).The learning and memory functions of each groups of mice were observed by Morris water maze test and Y maze test,and Aβimmunofluorescence staining was used to detect the deposition of Aβ in the hippocampus of each groups of mice to determine whether BDMC antagonized Aβ to modulate Alzheimer’s disease by regulating SCARA1.[Result]1.The results of water maze and Y maze showed that the correct alternation rate of APP/PS1 mice decreased and the latency increased,suggesting that their learning and memory ability decreased.The deposition of Aβ in the hippocampus of APP/PS1 mice increased,and the expression of SCARA1 was decreased compared with that of normal mice.It was found that the decreased Aβ clearance ability of AD mice may be related to the decreased expression of SCARA1.3.The expression of SCARA1 in APP/PS1 mice treated with Fucoidan was significantly lower than that in APP/PS1 mice,indicating that Fucoidan can inhibit the expression of SCARA1.2.BDMC intervention in the APP/PS1 group compared with the APP/PS1 group,the correct rate of Y maze increased,the latency of water maze shortened,the expression of SCARA1 in hippocampus increased,and the deposition of Aβ decreased,indicating that BDMC intervention can improve APP/PS1 mice.Learning and memory ability,reducing hippocampal Aβ deposition,while up-regulating SCARA1;3.The SCARA1 expression in the hippocampus of APP/PS1 mice treated with the SCARA1 inhibitor Fucoidan was significantly decreased,indicating that Fucoidan can effectively inhibit the expression of SCARA1;4.BDMC had no significant effect on the correct alternation rate,latency and Aβ deposition in hippocampus of Fuicoidan-treated APP/PS1 mice,indicating that Fuicoidan abolished the clearance of Aβ by BDMC and improved the learning and memory ability.[Conclusion]1.BDMC can antagonize AD in an in vivo test;2.One of the intrinsic mechanisms by which BDMC treats AD is to clear Aβ by up-regulating SCARA1.