DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice

Objective To explore whether the protein Deglycase protein 1(DJ1)can ameliorate Alzheimer’s disease(AD)-like pathology in Amyloid Precursor Protein/Presenilin 1(APP/PS1)double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.Methods Adeno-associated viral vectors(AAV)of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown.Mice were divided into the AD model control group(MC),AAV vector control group(NC),DJ1-overexpression group(DJ1+),and DJ1-knockdown group(DJ1-).After 21 days,the Morris water maze test,immunohistochemistry,immunofluorescence,and western blotting were used to evaluate the effects of DJ1 on mice.Results DJ1+overexpression decreased the latency and increased the number of platform traversals in the water maze test.DJ1-cells were cured and atrophied,and the intercellular structure was relaxed;the number of age spots and the expression of AD-related proteins were significantly increased.DJ1+increased the protein expression of Nuclear factor erythroid 2-related factor 2(NRF2),heme oxygenase-1(HO-1),light chain 3(LC3),phosphorylated AMPK(p-AMPK),and B cell lymphoma-2(BCL-2),as well as the antioxidant levels of total superoxide dismutase(T-SOD),total antioxidant capacity(T-AOC),and Glutathione peroxidase(GSH-PX),while decreasing the levels of Kelch-like hydrates-associated protein 1(Keap1),mammalian target of rapamycin(mTOR),p62/sequestosome1(p62/SQSTM1),Caspase3,and malondialdehyde(MDA).Conclusion DJ1-overexpression can ameliorate learning,memory,and AD-like pathology in APP/PS1 mice,which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.