Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease

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• 作者：Sha Liu^a ; Shuang-Qi Tang^a ; Heng-Jing Cui^a ; Sha Yin^a ; Ming Yin^b ; Hong Zhao^b ; Ling-Hua Meng^a ; Ze-Jian Wang^b ; ^{wangzejian@sjtu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Yang Lu^a ; ^{luyangssmu@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer's disease ; APPSWE/PS1M146V/TauP301L mouse model ; Dipotassium N-stearoyltyrosinate ; Animal behavior ; Neuroprotection
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：132
• 期：1
• 页码：92-99
• 全文大小：2447 K

文摘

Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)_SWE/presenilin-1 (PS1)_M146V/Tau_P301L mouse (3×Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms. NSTK could increase spontaneous locomotor activity in the open field and low anxiety-like behavior in the elevated plus maze, and improve the spatial memory deficits in the Morris water maze. The biochemical analysis suggested that NSTK could decrease Aβ₄₂ deposition, abnormal tau aggregation, and the expressions of p-APP Thr668, PS1 and p-tau Ser202/Thr205 in the hippocampus of 3×Tg-AD mice. Consistently, NSTK could reduce the level of malondialdehyde, increase the activity of superoxide dismutase and catalase. Up-regulation of Bcl-2, and down-regulation of BAX, caspase-3 and inflammatory cytokines also occurred in the hippocampus of 3×Tg-AD mice after treatment with NSTK. Thus, NSTK could intervene in multiple pathological processes of AD and would be a drug candidate against AD.