Alzheimer’s disease (AD) is globally recognized as a prominent cause of dementia for which efficient treatment is still lacking. New candidate compounds that are biologically potent are regularly tested. We, therefore, hypothesized to study the neuroprotective potential of Zinc Ortho Methyl Carbonodithioate (thereafter called ZOMEC) against Scopolamine (SCOP) induced Alzheimer’s disease (AD) model using adult albino mice. We post-administered ZOMEC (30 mg/Kg) into two group of mice for three weeks on daily basis that received either 0.9% saline or SCOP (1 mg/Kg) for initial two weeks. The other two groups of mice received 0.9% saline and SCOP (1 mg/Kg) respectively. After memory related behavioral analysis the brain homogenates were evaluated for the antioxidant potential of ZOMEC and multiple protein markers were examined through western blotting. Our results provide enough evidences that ZOMEC decrease oxidative stress by increasing catalase (CAT) and glutathione S transferase (GST) and decreasing the lipid peroxidation (LPO). The SIRT1 and pre and post synaptic marker proteins, synaptophysin (SYP) as well as post synaptic density protein (PSD-95) expression were also enhanced upon ZOMEC treatment. Furthermore, memory impairment was rescued and ZOMEC appreciably abrogated the Aβ accumulation, BACE1 expression C and the p-JNK pathway. The inflammatory protein markers, NF-kβ and IL-1β in ZOMEC treated mice were also comparable with control group. The predicted interaction of ZOMEC with SIRT1 was further confirmed by molecular docking. These findings thus provide initial reports on efficacy of ZOMEC in SCOP induced AD model.

Graphical Abstract

中文翻译：

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邻甲基二硫代碳锌通过 SIRT1/p-JNK 通路改善成年小鼠突触前和突触后记忆损伤

阿尔茨海默病（AD）是全球公认的痴呆症的主要原因，但目前仍缺乏有效的治疗方法。定期测试具有生物效力的新候选化合物。因此，我们假设使用成年白化小鼠研究邻甲基二硫代碳锌（以下称为 ZOMEC）对东莨菪碱 (SCOP) 诱导的阿尔茨海默病 (AD) 模型的神经保护潜力。我们将 ZOMEC (30 mg/Kg) 每天注射到两组小鼠体内三周，最初两周接受 0.9% 盐水或 SCOP (1 mg/Kg)。另外两组小鼠分别接受0.9%盐水和SCOP（1 mg/Kg）。在进行记忆相关行为分析后，评估了大脑匀浆的 ZOMEC 抗氧化潜力，并通过蛋白质印迹检查了多种蛋白质标记。我们的结果提供了足够的证据表明 ZOMEC 通过增加过氧化氢酶 (CAT) 和谷胱甘肽 S 转移酶 (GST) 以及减少脂质过氧化 (LPO) 来减少氧化应激。ZOMEC 治疗后，SIRT1 和突触前和突触后标记蛋白、突触素 (SYP) 以及突触后密度蛋白 (PSD-95) 的表达也得到增强。此外，记忆障碍得到了挽救，ZOMEC 明显消除了 Aβ 积累、BACE1 表达 C 和 p-JNK 通路。ZOMEC 治疗小鼠的炎症蛋白标志物 NF-kβ 和 IL-1β 也与对照组相当。通过分子对接进一步证实了 ZOMEC 与 SIRT1 的预测相互作用。因此，这些发现提供了 ZOMEC 在 SCOP 诱导的 AD 模型中功效的初步报告。

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