Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China.
Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China.
Int Immunopharmacol. 2024 Nov 15;141:112936. doi: 10.1016/j.intimp.2024.112936. Epub 2024 Aug 19.
Alzheimer's disease (AD) is a neurodegenerative disorder that is difficult to cure and of global concern. Neuroinflammation is closely associated with the onset and progression of AD, making its treatment increasingly important. Compounds from natural products, with fewer side effects than synthetic drugs, are of high research interest. STAT3, a multifunctional transcription factor, is involved in various cellular processes including inflammation, cell growth, and apoptosis. Its activation and inhibition can have different effects under various pathological conditions. In AD, the STAT3 protein plays a crucial role in promoting neuroinflammation and contributing to disease progression. This occurs primarily through the JAK2-STAT3 signaling pathway, which impacts microglia, astrocytes, and hippocampal neurons. This paper reviews the STAT3 signaling pathway in AD and 25 compounds targeting STAT3 up to 2024. Notably, Rutin, Paeoniflorin, and Geniposide up-regulate STAT3 in hippocampal and cortex neurons, showing neuroprotective effects in various AD models. Other 23 compounds downregulate AD by suppressing neuroinflammation through inhibition of STAT3 activation in microglia and astrocytes. These findings highlight the potential of compounds from natural products in improving AD by targeting STAT3, offering insights into the prevention and management of AD.
阿尔茨海默病（AD）是一种难以治愈的神经退行性疾病，引起了全球关注。神经炎症与 AD 的发病和进展密切相关，因此其治疗变得越来越重要。与合成药物相比，天然产物中的化合物副作用更少，因此受到了高度的研究关注。STAT3 是一种多功能转录因子，参与包括炎症、细胞生长和细胞凋亡在内的多种细胞过程。其激活和抑制在不同的病理条件下会产生不同的影响。在 AD 中，STAT3 蛋白在促进神经炎症和促进疾病进展方面起着至关重要的作用。这主要是通过 JAK2-STAT3 信号通路发生的，该信号通路会影响小胶质细胞、星形胶质细胞和海马神经元。本文综述了 AD 中 STAT3 信号通路以及截至 2024 年针对 STAT3 的 25 种化合物。值得注意的是，芦丁、芍药苷和栀子苷在海马和皮质神经元中上调 STAT3，在各种 AD 模型中表现出神经保护作用。其他 23 种化合物通过抑制小胶质细胞和星形胶质细胞中 STAT3 的激活来抑制神经炎症，从而改善 AD。这些发现强调了天然产物化合物通过靶向 STAT3 改善 AD 的潜力，为 AD 的预防和管理提供了新的思路。
