Abstract:

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 stria-tal-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocam-pus 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 phos-phorylation 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 stri-atal-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, stria-tal-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alz-heimer’s disease.

Key words: neural regeneration, brain injury, neurodegeneration, Alzheimer’s disease, striatal-enriched phos-phatase 61, amyloid-beta peptide, N-methyl-D-aspartate receptor, GluN2B, RNA interference, im-munohistochemistry, western blot, neuroregeneration