World Journal of
Pharmaceutical and Life Sciences

TETRAMETHYLPYRAZINE DIMER ALLEVIATES APP PROCESSING AND TAU HYPERPHOSPHORYLATION IN NEURO2A/APPSWE CELLS

*Xiaoyi Lin, Xifei Yang* and Xianfeng Huang*

ABSTRACT

Alzheimer's disease (AD) is a common neurodegenerative disease whose two major pathological features are ?-amyloid (A?) aggregation and tau hyperphosphorylation. Tetramethylpyrazine is an alkaloid monomer extracted from Chuanxiong, which has specific pharmacological effects such as improving learning and memory and protecting nerves. Here, we evaluated the neuroprotective effect of a newly synthesized tetramethylpyrazine dimer (DTMP) using the murine neuron-like cells (N2a) transfected with the human "Swedish" mutant amyloid precursor protein (N2aAPP). the half-inhibitory concentration (IC50) of DTMP against N2a/APPswe cells was 12.37 ?M as measured by cell proliferation-toxicity assay (CCK-8). Western blot analysis showed that DTMP treatment significantly reduced the expression of BACE1, PS1 and t-APP in the APP pathway and attenuated the phosphorylation levels of Ser396, Ser262 and Thr231 in Tau protein. The modulation of dysregulated proteins implicated in AD pathogenesis implies the pharmacological mechanisms of DTMP and its potential as a novel therapeutic choice in AD.

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