Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-03-09 DOI:10.1111/cns.70329

Jianhui Su, Lanyang Zhao, Runze Fu, Zhe Tang

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Abstract

Background

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.

Method

We systematically review the latest research on the pathogenesis and therapeutic strategies of AD in PubMed, Web of Science, and Elsevier SD.

Result

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 Ca²⁺-ATPase (SERCA) that influence SERCA to release Ca²⁺ mediating inflammation were also reviewed.

Conclusion

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.

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阿尔茨海默病中与内质网应激相关的肠-脑轴脂质代谢与昼夜节律的联系

阿尔茨海默病（AD）的特点是认知、学习和记忆能力下降。神经炎症与阿尔茨海默病新皮层中tau缠结的扩散有关，导致认知障碍。因此，明确神经炎症的发病机制，寻找有效的治疗方法是AD临床治疗的关键问题。方法系统回顾PubMed、Web of Science和Elsevier SD上关于AD发病机制和治疗策略的最新研究。结果探讨了昼夜节律介导的肠-脑轴脂质代谢对AD的作用机制，并分析了脂质异常引起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，还强调了脂质稳态（磷脂、脂肪酸、甾醇）在维持内质网功能中的重要性。同时，由于脂质成分影响蛋白质构象，对肌浆网Ca2+- atp酶（SERCA）周围膜磷脂影响SERCA释放Ca2+介导炎症也进行了综述。结论研究了脂质微结构域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、肠黏膜和脑信号通路在AD发病中的作用，并提出了通过改变饮食脂质措施来预防AD的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.