The formation of neurofibrillary tangles has been implicated as an important pathological marker for Alzheimer’s disease (AD). Studies have revealed that the inhibition of abnormal hyperphosphorylation and aggregation of tau in the AD brain might serve as an important drug target. Using in vitro and in vivo experimental models, such as the AD mouse model (5xFAD mice), we investigated the inhibition of hyperphosphorylation of tau using the human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Administration of hUCB-MSCs not only ameliorated the spatial learning and memory impairments but also mitigated the hyperphosphorylation of tau in 5xFAD mice. Furthermore, in vivo experiments in mice and in vitro ThT fluorescence assay validated galectin-3 (GAL-3) as an essential factor of hUCB-MSC. Moreover, GAL-3 was observed to be involved in the removal of aberrant forms of tau, by reducing hyperphosphorylation through decrements in the glycogen synthase kinase 3 beta (GSK-3β). Our results confirm that GAL-3, secreted by hUCB-MSC, regulates the abnormal accumulation of tau by protein-protein interactions. This study suggests that hUCB-MSCs mitigate hyperphosphorylation of tau through GAL-3 secretion. These findings highlight the potential role of hUCB-MSCs as a therapeutic agent for aberrant tau in AD.

中文翻译：

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人脐带血间充质干细胞分泌的半乳凝素3减少了阿尔茨海默病模型中异常的Tau磷酸化。

神经原纤维缠结的形成已被认为是阿尔茨海默氏病（AD）的重要病理标志。研究表明，在AD脑中抑制tau蛋白异常磷酸化和聚集可能是重要的药物靶标。使用体外和体内实验模型，例如AD小鼠模型（5xFAD小鼠），我们研究了使用人脐带血来源的间充质干细胞（hUCB-MSC）对tau过度磷酸化的抑制作用。hUCB-MSCs的施用不仅改善了空间学习和记忆障碍，而且减轻了5xFAD小鼠中tau的过度磷酸化。此外，在体内实验中小鼠和体外ThT荧光检测验证了galectin-3（GAL-3）是hUCB-MSC的必要因子。此外，GAL-3中观察到参与去除tau的异常形式，通过在糖原合酶减量减少过度磷酸激酶3β（GSK-3 β）。我们的结果证实，hUCB-MSC分泌的GAL-3通过蛋白-蛋白相互作用调节tau的异常积累。这项研究表明，hUCB-MSC通过GAL-3分泌减轻tau的过度磷酸化。这些发现突显了hUCB-MSC作为AD中异常tau的治疗剂的潜在作用。