(1) We investigated the mechanism of action of striatal-enriched phosphatase 61 at the behavioral and signaling molecule levels, using in vivo and in vitro models. We discussed the relationship of striatal-enriched phosphatase 61 with transgene and N-methyl-D-aspartate receptor 2B, and lyzed the molecular mechanism by which striatal-enriched phosphatase 61 regulates N-methyl-D-aspartate receptor 2B transport.Research Highlights
(2) Spatial learning and memory deficits in Alzheimer's disease may be associated with disturbed N-methyl-D-aspartate receptor 2B transport caused by striatal-enriched phosphatase 61. RNA silencing can effectively inhibit striatal-enriched phosphatase 61 target gene expression and can be used to investigate the function and involvement of striatal-enriched phosphatase 61 in the pathogenesis of Alzheimer's disease.Research Highlights
(3) This study provides a basic reference for gene therapy for Alzheimer's disease using striatal-enriched phosphatase 61.
To stop the progression of Alzheimer's disease in the early stage, it is necessary to identify new therapeutic targets. We examined striatal-enriched phosphatase 61 expression in the brain tissues of 12-month-old APPswe/PSEN1dE9 transgenic mice. Immunohistochemistry showed that al-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocampus of APPswe/PSEN1dE9 transgenic mice. Western blotting of a cell model of Alzheimer's disease consisting of amyloid-beta peptide (1-42)-treated C57BL/6 mouse cortical neurons in vitro showed that valeric acid (AP5), an N-methyl-D-aspartate receptor antagonist, significantly inhibited amyloid-beta 1-42-induced increased activity of striatal-enriched phosphatase 61. In addition, the phosphorylation of N-methyl-D-aspartate receptor 2B at Tyr1472 was impaired in amyloid-beta 1-42-treated cortical neurons, but knockdown of striatal-enriched phosphatase 61 enhanced the phosphorylation of N-methyl-D-aspartate receptor 2B. Collectively, these findings indicate that striatal-enriched phosphatase 61 can disturb N-methyl-D-aspartate receptor transport and inhibit the progression of learning and study disturbances induced by Alzheimer's disease. Thus, al-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alzheimer's disease.