Tβ4 reverses glial polarization and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PSI mice

Tβ4 plays an important role in the control of actin polymerization in eukaryotic cells.While its effect in multiple organs and diseases has being widely investigated,lttle is known about its influence on Alzheimer's disease and the possible mechanisms.Thus,we aimed to evaluate the effects and mechanisms of T94 on glial polarization and cognitive performance in APP/PS1 transgenic mice.Morris water maze test were conducted to assess memory in APP/PS1 mice.Thioflavin S staining,IHC/IF,ELISA,and immunoblotting were performed to explore Aβaccumulation,glial polarization and TLR4/NF-rB axis.We demonstrated that over expression of T94 alone alleviated Aβaccumulation of APP/PS1 mice,reversed microglia and astrocyte polarization and cognitive behavior performance.In addition,Tβ4 could downregulate both TLR4/MyD88/NF-xB p65 and p52 dependent inflammatory pathway.While combination drug of TLR4 antagonist or NF-rB p65 inhibitor exerted no further effects.