Abstract：
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.
摘要：
阿尔茨海默病（AD）与血管功能障碍之间的紧密关系已成为老龄化社会日益关注的焦点。在本研究中,我们研究了扇贝衍生的缩醛磷脂(sPlas)对脑低灌注(HP)AD小鼠模型脑内血管重塑相关蛋白的长期影响.我们证明了,第一次,脑HP激活了晚期糖基化终产物受体（RAGE）/磷酸化信号转导和转录激活因子3（pSTAT3）/莫洛尼鼠白血病病毒1（PIM1）/活化T细胞核因子1（NFATc1）的前病毒整合位点，解释了这种脑血管重塑。此外，我们还发现脑HP加速了pSTAT3介导的星形胶质细胞增生和核苷酸结合域和富含亮氨酸重复蛋白3（NLRP3）炎性体的激活，可能导致认知能力下降。另一方面,sPlas治疗减弱了独立于RAGE的pSTAT3/PIM1/NFATc1轴的激活，并显着抑制了NLRP3炎性体的激活，证明对AD的有益作用。
