载脂蛋白 E4 相关痴呆症中的脂质与脑炎症。
Lipids and brain inflammation in APOE4-associated dementia.
机构信息
Department of Radiology, Keck School of Medicine.
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy.
出版信息
Curr Opin Lipidol. 2022 Feb 1;33(1):16-24. doi: 10.1097/MOL.0000000000000801.
PURPOSE OF REVIEW
To highlight recent developments in studying mechanisms by which the apolipoprotein E4 (APOE4) allele affects the metabolism of brain lipids and predisposes the brain to inflammation and Alzheimer's disease (AD) dementia.
RECENT FINDINGS
APOE4 activates Ca2+ dependent phospholipase A2 (cPLA2) leading to changes in arachidonic acid (AA), eicosapentaenoic acid and docosahexaenoic acid signaling cascades in the brain. Among these changes, the increased conversion of AA to eicosanoids associates with sustained and unresolved chronic brain inflammation. The effects of APOE4 on the brain differ by age, disease stage, nutritional status and can be uncovered by brain imaging studies of brain fatty acid uptake. Reducing cPLA2 expression in the dementia brain presents a viable strategy that awaits to be tested.
SUMMARY
Fatty acid brain imaging techniques can clarify how changes to brain polyunsaturated fatty acid metabolism during the various phases of AD and guide the development of small molecules to mitigate brain inflammation.
目的综述
强调研究载脂蛋白 E4 (APOE4) 等位基因如何影响脑脂质代谢并使大脑易患炎症和阿尔茨海默病 (AD) 痴呆的机制方面的最新进展。
最近的发现
APOE4 激活 Ca2+ 依赖性磷脂酶 A2 (cPLA2)，导致大脑中花生四烯酸 (AA)、二十碳五烯酸和二十二碳六烯酸信号级联的变化。在这些变化中，AA 向类二十烷酸的转化增加与持续和未解决的慢性脑炎症有关。APOE4 对大脑的影响因年龄、疾病阶段、营养状况而异，可以通过脑脂肪酸摄取的脑成像研究来揭示。降低痴呆大脑中的 cPLA2 表达是一种可行的策略，有待进一步验证。
总结
脂肪酸脑成像技术可以阐明 AD 各个阶段大脑多不饱和脂肪酸代谢的变化，并指导开发小分子来减轻脑炎症。
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