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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引用次数: 0

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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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.