A strong relationship between Alzheimer’s disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD.

中文翻译：

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扇贝缩醛磷脂通过 pSTAT3/PIM1/NFATc1 轴在阿尔茨海默病脑灌注不足的新型小鼠模型中对血管功能障碍的保护作用

阿尔茨海默病（AD）与血管功能障碍之间的密切关系已成为老龄化社会日益关注的焦点。在本研究中，我们研究了扇贝缩醛磷脂 (sPlas) 对 AD 脑灌注不足 (HP) 小鼠模型大脑中血管重塑相关蛋白的长期影响。我们首次证明，脑 HP 激活了晚期糖基化终末产物 (RAGE) 受体轴/磷酸化信号转导器和转录激活剂 3 (pSTAT3)/莫洛尼鼠白血病病毒 1 (PIM1)/原病毒整合位点/活化T细胞核因子1 (NFATc1)，负责这种脑血管重塑。此外，我们还发现脑 HP 加速了 pSTAT3 介导的星形胶质细胞增生以及核苷酸结合域和富含亮氨酸重复蛋白 3 (NLRP3) 炎症小体的激活，可能导致认知能力下降。另一方面，sPlas 治疗可独立于 RAGE 减弱 pSTAT3/PIM1/NFATc1 轴的激活，并显着抑制 NLRP3 炎性体激活，证明对 AD 具有有益作用。