Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Department of Pharmacy, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China.
CNS Neurosci Ther. 2024 Nov;30(11):e70127. doi: 10.1111/cns.70127.
Many factors affect the neuroinflammatory response in patients with Alzheimer disease (AD). Galectin-3 (Gal-3) is closely related to microglial activation in the nervous system and can promote the aggregation of cancer cells in tumors. This study aimed to investigate the mechanism by which farnesylthiosalicylic acid (FTS) affects neuroinflammation in Aβ mice through Gal-3.
We used the Morris water maze, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence to conduct our study.
FTS reduced the levels of proinflammatory factors and microglial activation in Aβ mice. FTS inhibited total and membrane expression levels of Gal-3 in Aβ mice, and the anti-inflammatory effect of FTS was reversed by Gal-3-adeno-associated viral (AAV). FTS reduced the expression levels of toll-like receptors (TLRs), effects that were reversed by Gal-3-AAV. Moreover, FTS ameliorated Aβ oligomerization and accumulation in Aβ mice, effects that were also reversed by Gal-3-AAV. FTS, through the inhibition of the Gal-3-c-Jun N-terminal kinase (JNK) pathway, reduced PS1 expression; in addition, inhibition of Gal-3 increased the Aβ-degrading enzymes in Aβ mice. FTS-induced improvements in cognition in Aβ mice were reversed by Gal-3-AAV.
FTS may through inhibiting Gal-3 reduce the expression of TLR4 and CD14 and alleviate Aβ pathology, downregulating Aβ-stimulated TLR2, TLR4, and CD14 expression, and thus alleviate neuroinflammation in Aβ mice.
许多因素会影响阿尔茨海默病（AD）患者的神经炎症反应。半乳糖凝集素-3（Gal-3）与神经系统中的小胶质细胞激活密切相关，并能促进肿瘤中癌细胞的聚集。本研究旨在通过 Gal-3 探讨法尼醇硫代水杨酸（FTS）影响 Aβ 小鼠神经炎症的机制。
我们使用 Morris 水迷宫、逆转录-聚合酶链反应（RT-PCR）、Western blot、酶联免疫吸附测定（ELISA）和免疫荧光来进行研究。
FTS 降低了 Aβ 小鼠促炎因子和小胶质细胞激活水平。FTS 抑制了 Aβ 小鼠中 Gal-3 的总表达和膜表达水平，Gal-3 腺相关病毒（AAV）逆转了 FTS 的抗炎作用。FTS 降低了 Toll 样受体（TLRs）的表达水平，Gal-3 AAV 逆转了这一作用。此外，FTS 改善了 Aβ 寡聚体和积累在 Aβ 小鼠中的表达水平，Gal-3 AAV 也逆转了这一作用。FTS 通过抑制 Gal-3-c-Jun N-末端激酶（JNK）通路降低 PS1 表达；此外，抑制 Gal-3 增加了 Aβ 小鼠中的 Aβ 降解酶。Gal-3 AAV 逆转了 FTS 诱导的 Aβ 小鼠认知改善。
FTS 可能通过抑制 Gal-3 减少 TLR4 和 CD14 的表达，减轻 Aβ 病理，下调 Aβ 刺激的 TLR2、TLR4 和 CD14 的表达，从而减轻 Aβ 小鼠的神经炎症。
