Currently, no treatments exist that are able to directly treat against Alzheimer's disease (AD), and we are facing an inevitable increase in the near future of the amount of patients who will suffer from AD. Most animal models of AD are limited by not being able to recapitulate the entire pathology of AD. Recently an AD model in zebrafish was established by using the protein phosphatase 2A inhibitor, okadaic acid (OKA). Administering OKA to zebrafish was able to recapitulate most of the neuropathology associated with AD. Therefore, providing a drug discovery model for AD that is also time and cost efficient. This study was designed to investigate the effects of GSK3β inhibition by 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8) on this newly developed AD model. Fish were divided into 4 groups and each group received a different treatment. The fish were divided into a control group, a group treated with 1 μM TDZD-8 only, a group treated with 1 μM TDZD-8 + 100 nM OKA, and a group treated with 100 nM OKA only. Administering the GSK3β inhibitor to zebrafish concomitantly with OKA proved to be protective. TDZD-8 treatment reduced the mortality rate, the ratio of active: inactive GSK3β, pTau (Ser199), and restored PP2A activity. This further corroborates the use of GSKβ inhibitors in the treatment against AD and bolsters the use of the OKA-induced AD-like zebrafish model for drug discovery.

中文翻译：

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GSK3β抑制剂TDZD-8可以恢复冈田酸诱发的阿尔茨海默氏病的斑马鱼模型中的认知。

当前，尚无能够直接治疗阿尔茨海默氏病（AD）的治疗方法，并且在不久的将来，我们将面临不可避免的AD病患者数量的增长。大多数AD动物模型由于不能概括AD的整个病理而受到限制。最近，通过使用蛋白磷酸酶2A抑制剂冈田酸（OKA）建立了斑马鱼的AD模型。对斑马鱼使用OKA可以概括与AD相关的大多数神经病理。因此，提供一种既节省时间又节省成本的用于AD的药物发现模型。这项研究旨在研究4-苄基-2-甲基-1、2、4-噻二唑烷-3、5-二酮（TDZD-8）对GSK3β的抑制作用对这种新开发的AD模型的影响。将鱼分为4组，每组接受不同的处理。将鱼分成对照组，仅用1μMTDZD-8处理的组，用1μMTDZD-8 + 100nM OKA处理的组和仅用100nM OKA处理的组。证明将GSK3β抑制剂与OKA并用对斑马鱼有保护作用。TDZD-8治疗降低了死亡率，降低了活性GSK3β与非活性GSK3β，pTau（Ser199）的比例，并恢复了PP2A活性。这进一步证实了GSKβ抑制剂在抗AD的治疗中的应用，并加强了OKA诱导的AD样斑马鱼模型在药物发现中的应用。证明将GSK3β抑制剂与OKA并用对斑马鱼有保护作用。TDZD-8治疗降低了死亡率，降低了活性GSK3β与非活性GSK3β，pTau（Ser199）的比例，并恢复了PP2A活性。这进一步证实了GSKβ抑制剂在抗AD的治疗中的应用，并加强了OKA诱导的AD样斑马鱼模型在药物发现中的应用。证明将GSK3β抑制剂与OKA并用对斑马鱼有保护作用。TDZD-8治疗降低了死亡率，降低了活性GSK3β与非活性GSK3β，pTau（Ser199）的比例，并恢复了PP2A活性。这进一步证实了GSKβ抑制剂在抗AD的治疗中的应用，并加强了OKA诱导的AD样斑马鱼模型在药物发现中的应用。