Abstract
BACKGROUND: Alzheimer's Disease (AD) is one of common progressive and fatal neurodegenerative disorders,and its main clinical symptoms are progressive memory impairment and cognitive dysfunction. The Tat-NR2B9c, a peptide was known as postsynaptic density protein-95(PSD-95) inhibitors, has shown clinical efficacy as a neuroprotective effects in some diseases such as acute stroke and neuropathic pain.The aim of the study is to clarify whether Tat-NR2B9c has the same neuroprotective effects in AD. METHODS: Studies were performed in mice modeling AD induced by Aβ(1-42). Animals were treated with drugs after modeling AD for 14 days,and the spatial learning and memory ability were assessed after drug treatment. Then, mice were euthanized for biochemical tests. RESULTS: The levels of PSD-95 and NR2B decreased,and the levels of N-methyl-d-aspartate receptor-postsynaptic density protein-95 interaction increased in hippocampus in AD mice. Tat-NR2B9c can improve spatial learning and memory ability in AD mice by perturbing PSD-95 interactions with NR2B-subtype but not inhibiting PSD-95 levels. CONCLUSION: Tat-NR2B9c can prevent cognitive dysfunction in mice modeling AD induced by Aβ1-42 via perturbing PSD-95 interactions with NR2B-subtype receptors.