Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by Aβ1–42 via perturbing PSD-95 interactions with NR2B-subtype receptors

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.