Su Jianhui, Zhao Lanyang, Fu Runze, Tang Zhe
School of Marine and Bioengineering, Yancheng Institute of Technology, Yancheng, Jiangsu, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
CNS Neurosci Ther. 2025 Mar;31(3):e70329. doi: 10.1111/cns.70329.
Alzheimer's disease (AD) is characterized by a decline in cognitive, learning, and memory abilities. Neuroinflammation is associated with the spread of tau tangles in the neocortex of AD, leading to cognitive impairment. Therefore, clarifying the pathogenesis of Neuroinflammation and finding effective treatments are the crucial issues for the clinical management of AD.
We systematically review the latest research on the pathogenesis and therapeutic strategies of AD in PubMed, Web of Science, and Elsevier SD.
In this review, the mechanism of the effect of gut-brain axis lipid metabolism mediated by circadian rhythm on AD was discussed, and we also analysed the effects of inflammation and endoplasmic reticulum stress (ERS) induced by lipid abnormalities on intestinal mucosal barrier and neurodegeneration; furthermore, the importance of lipid homeostasis (phospholipids, fatty acids, sterol) in maintaining the functions of endoplasmic reticulum was emphasized. Meanwhile, as lipid composition affects protein conformation, the membrane phospholipids surrounding sarcoplasmic reticulum Ca-ATPase (SERCA) that influence SERCA to release Ca mediating inflammation were also reviewed.
We interpreted the mechanism of action between lipid microdomains and ER membrane proteins, reviewed the role of the new pathway of circadian rhythm, lipid metabolism, intestinal mucosa, and brain signaling in the pathogenesis of AD, and proposed strategies to prevent AD by changing the dietary lipid measures.
阿尔茨海默病（AD）的特征是认知、学习和记忆能力下降。神经炎症与AD新皮质中tau缠结的扩散有关，导致认知障碍。因此，阐明神经炎症的发病机制并找到有效的治疗方法是AD临床管理的关键问题。
我们在PubMed、科学网和爱思唯尔SD中系统回顾了关于AD发病机制和治疗策略的最新研究。
在本综述中，讨论了昼夜节律介导的肠-脑轴脂质代谢对AD的影响机制，我们还分析了脂质异常诱导的炎症和内质网应激（ERS）对肠黏膜屏障和神经退行性变的影响；此外，强调了脂质稳态（磷脂、脂肪酸、固醇）在维持内质网功能中的重要性。同时，由于脂质组成影响蛋白质构象，还综述了肌浆网Ca-ATP酶（SERCA）周围的膜磷脂影响SERCA释放Ca介导炎症的作用。
我们解释了脂质微区与内质网膜蛋白之间的作用机制，综述了昼夜节律、脂质代谢、肠黏膜和脑信号传导新途径在AD发病机制中的作用，并提出了通过改变饮食脂质措施预防AD的策略。
