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Navigating the metabolic maze: anomalies in fatty acid and cholesterol processes in Alzheimer’s astrocytes

Zhang, Xiaoyu, Chen, Chuanying, Liu, Yi·2024·Alzheimer's Research & Therapy
DOI 10.1186/s13195-024-01430-xPMC PMC10960454
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Abstract

Alzheimer’s disease (AD) is the most common cause of dementia, and its underlying mechanisms have been a subject of great interest. The mainstream theory of AD pathology suggests that the disease is primarily associated with tau protein and amyloid-beta (Aβ). However, an increasing body of research has revealed that abnormalities in lipid metabolism may be an important event throughout the pathophysiology of AD. Astrocytes, as important members of the lipid metabolism network in the brain, play a significant role in this event. The study of abnormal lipid metabolism in astrocytes provides a new perspective for understanding the pathogenesis of AD. This review focuses on the abnormal metabolism of fatty acids (FAs) and cholesterol in astrocytes in AD, and discusses it from three perspectives: lipid uptake, intracellular breakdown or synthesis metabolism, and efflux transport. We found that, despite the accumulation of their own fatty acids, astrocytes cannot efficiently uptake fatty acids from neurons, leading to fatty acid accumulation within neurons and resulting in lipotoxicity. In terms of cholesterol metabolism, astrocytes exhibit a decrease in endogenous synthesis due to the accumulation of exogenous cholesterol. Through a thorough investigation of these metabolic abnormalities, we can provide new insights for future therapeutic strategies by literature review to navigate this complex metabolic maze and bring hope to patients with Alzheimer’s disease.

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Metadata

Authors
Zhang, X., Chen, C., & Liu, Y.
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2024-03-23
Volume
16
Issue
1
ISSN
1758-9193
DOI
10.1186/s13195-024-01430-x
PMC
PMC10960454
Cited by
34
References
22
Language
en
Licence
Funders
National Natural Science Foundation of China (82103033, 82002646, and 81972352)

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