中枢神经系统中的脂蛋白：从生物学到病理生物学。
Lipoproteins in the Central Nervous System: From Biology to Pathobiology.
机构信息
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA; email:
出版信息
Annu Rev Biochem. 2022 Jun 21;91:731-759. doi: 10.1146/annurev-biochem-032620-104801. Epub 2022 Mar 18.
Abstract
The brain, as one of the most lipid-rich organs, heavily relies on lipid transport and distribution to maintain homeostasis and neuronal function. Lipid transport mediated by lipoprotein particles, which are complex structures composed of apolipoproteins and lipids, has been thoroughly characterized in the periphery. Although lipoproteins in the central nervous system (CNS) were reported over half a century ago, the identification of as the strongest genetic risk factor for Alzheimer's disease has accelerated investigation of the biology and pathobiology of lipoproteins in the CNS. This review provides an overview of the different components of lipoprotein particles, in particular apolipoproteins, and their involvements in both physiological functions and pathological mechanisms in the CNS.
摘要
大脑作为脂质含量最丰富的器官之一，严重依赖于脂质的运输和分布来维持其体内平衡和神经元功能。由载脂蛋白和脂质组成的脂蛋白颗粒介导的脂质运输在外周组织中得到了深入研究。尽管半个多世纪前就已经报道了中枢神经系统（CNS）中的脂蛋白，但作为阿尔茨海默病最强遗传风险因素的 的发现，加速了对 CNS 中脂蛋白的生物学和病理生物学的研究。本综述概述了脂蛋白颗粒的不同成分，特别是载脂蛋白，以及它们在 CNS 的生理功能和病理机制中的作用。
相似文献
1
Lipoproteins in the Central Nervous System: From Biology to Pathobiology.中枢神经系统中的脂蛋白：从生物学到病理生物学。
Annu Rev Biochem. 2022 Jun 21;91:731-759. doi: 10.1146/annurev-biochem-032620-104801. Epub 2022 Mar 18.
2
Purification and characterization of astrocyte-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice.从野生型和人载脂蛋白E转基因小鼠中纯化并鉴定星形胶质细胞分泌的含载脂蛋白E和J的脂蛋白。
Neurochem Int. 2001 Nov-Dec;39(5-6):415-25. doi: 10.1016/s0197-0186(01)00049-3.
3
Brain lipoprotein metabolism and its relation to neurodegenerative disease.脑脂蛋白代谢及其与神经退行性疾病的关系。
Crit Rev Neurobiol. 1999;13(4):357-407. doi: 10.1615/critrevneurobiol.v13.i4.20.
4
Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice.野生型、载脂蛋白E（apoE）基因敲除（-/-）小鼠以及人载脂蛋白E转基因小鼠的原代星形胶质细胞分泌的独特脂蛋白。
J Biol Chem. 1999 Oct 15;274(42):30001-7. doi: 10.1074/jbc.274.42.30001.
5
ApoE: crossroads between Alzheimer's disease and atherosclerosis.载脂蛋白E：阿尔茨海默病与动脉粥样硬化的交叉点。
Semin Vasc Med. 2004 Aug;4(3):279-85. doi: 10.1055/s-2004-861496.
6
Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins.载脂蛋白E等位基因对人脑脊液载脂蛋白的影响。
J Lipid Res. 1998 Dec;39(12):2443-51.
7
[The role of lipid metabolism in Alzheimer's disease].[脂质代谢在阿尔茨海默病中的作用]
Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Aug;22(4):103-10.
8
APOE and Alzheimer's Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer's Pathogenesis.载脂蛋白 E 与阿尔茨海默病：越来越多的证据表明，针对载脂蛋白 E4 可能有助于对抗阿尔茨海默病的发病机制。
Mol Neurobiol. 2019 Apr;56(4):2450-2465. doi: 10.1007/s12035-018-1237-z. Epub 2018 Jul 21.
9
The cell biology of APOE in the brain.载脂蛋白 E 在大脑中的细胞生物学。
Trends Cell Biol. 2024 Apr;34(4):338-348. doi: 10.1016/j.tcb.2023.09.004. Epub 2023 Oct 5.
10
CSF lipoproteins and Alzheimer's disease.脑脊液脂蛋白与阿尔茨海默病
J Nutr Health Aging. 2002;6(6):383-91.
引用本文的文献
1
A Conserved FABP5 Macrophage Subset Promotes Fibrosis and Carcinogenesis in Advanced Liver Disease.一种保守的FABP5巨噬细胞亚群促进晚期肝病中的纤维化和致癌作用。
Liver Int. 2025 Sep;45(9):e70262. doi: 10.1111/liv.70262.
2
Structural analyses define the molecular basis of clusterin chaperone function.结构分析确定了簇集素伴侣功能的分子基础。
Nat Struct Mol Biol. 2025 Aug 8. doi: 10.1038/s41594-025-01631-4.
3
Cholesterol in the CNS: functions, recycling and remyelination.中枢神经系统中的胆固醇：功能、循环利用与髓鞘再生
J Neuroinflammation. 2025 Jul 11;22(1):180. doi: 10.1186/s12974-025-03490-8.
4
Triglycerides are an important fuel reserve for synapse function in the brain.甘油三酯是大脑中突触功能的重要燃料储备。
Nat Metab. 2025 Jul 1. doi: 10.1038/s42255-025-01321-x.
5
APOE Genotype Impacts Polyunsaturated Neutral Lipid Storage and Ferroptosis Vulnerability in Astrocytes.APOE基因分型影响星形胶质细胞中多不饱和中性脂质的储存和铁死亡易感性。
Neurochem Res. 2025 Jun 26;50(4):211. doi: 10.1007/s11064-025-04463-2.
6
Interactions between TTYH2 and APOE facilitate endosomal lipid transfer.TTYH2与载脂蛋白E之间的相互作用促进内体脂质转移。
Nature. 2025 Jun 25. doi: 10.1038/s41586-025-09200-x.
7
Human placental extract rescues hippocampal damage associated with cognitive impairment in diabetic male rats through antioxidative, anti-inflammatory, and neuromodulatory activities.人胎盘提取物通过抗氧化、抗炎和神经调节活性挽救糖尿病雄性大鼠与认知障碍相关的海马损伤。
Metab Brain Dis. 2025 Jun 16;40(6):225. doi: 10.1007/s11011-025-01646-2.
8
Broken Balance: Emerging Cross-Talk Between Proteostasis and Lipostasis in Neurodegenerative Diseases.失衡：神经退行性疾病中蛋白质稳态与脂质稳态之间新出现的相互作用
Cells. 2025 Jun 4;14(11):845. doi: 10.3390/cells14110845.
9
Alzheimer's disease pathogenesis: standing at the crossroad of lipid metabolism and immune response.阿尔茨海默病发病机制：处于脂质代谢与免疫反应的十字路口
Mol Neurodegener. 2025 Jun 4;20(1):67. doi: 10.1186/s13024-025-00857-6.
10
ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.载脂蛋白E4（ApoE4）需要增强脂化作用，以解决NPC1抑制后细胞内脂质和蛋白质异常的问题。
Sci Rep. 2025 Apr 29;15(1):15051. doi: 10.1038/s41598-025-96531-4.
本文引用的文献
1
-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia.杰克逊维尔（V236E）变异体降低了自聚集和痴呆风险。
Sci Transl Med. 2021 Sep 29;13(613):eabc9375. doi: 10.1126/scitranslmed.abc9375.
2
Protective genes and pathways in Alzheimer's disease: moving towards precision interventions.阿尔茨海默病中的保护性基因和通路：走向精准干预。
Mol Neurodegener. 2021 Apr 29;16(1):29. doi: 10.1186/s13024-021-00452-5.
3
Beyond association: successes and challenges in linking non-coding genetic variation to functional consequences that modulate Alzheimer's disease risk.超越关联：将非编码遗传变异与调节阿尔茨海默病风险的功能后果联系起来的成功和挑战。
Mol Neurodegener. 2021 Apr 21;16(1):27. doi: 10.1186/s13024-021-00449-0.
4
Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia.选择性清除星形胶质细胞 APOE4 能强烈阻止 tau 介导的神经退行性变，并减少小胶质细胞的突触吞噬作用。
Neuron. 2021 May 19;109(10):1657-1674.e7. doi: 10.1016/j.neuron.2021.03.024. Epub 2021 Apr 7.
5
Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer's disease.胆固醇通过损害阿尔茨海默病中的视神经萎缩症相关蛋白 5 募集和溶酶体清除来改变线粒体自噬。
Mol Neurodegener. 2021 Mar 8;16(1):15. doi: 10.1186/s13024-021-00435-6.
6
APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function.载脂蛋白 E 免疫疗法可减少脑淀粉样血管病和淀粉样斑块，同时改善脑血管功能。
Sci Transl Med. 2021 Feb 17;13(581). doi: 10.1126/scitranslmed.abd7522.
7
Apolipoprotein E4 Reduction with Antisense Oligonucleotides Decreases Neurodegeneration in a Tauopathy Model.使用反义寡核苷酸降低载脂蛋白E4可减少tau蛋白病模型中的神经退行性变。
Ann Neurol. 2021 May;89(5):952-966. doi: 10.1002/ana.26043. Epub 2021 Feb 24.
8
Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology.星形胶质细胞分泌的聚集素促进兴奋性突触传递，并改善阿尔茨海默病的神经病理学。
Mol Neurodegener. 2021 Jan 31;16(1):5. doi: 10.1186/s13024-021-00426-7.
9
Comprehensive metabolic profiling of Parkinson's disease by liquid chromatography-mass spectrometry.采用液相色谱-质谱联用技术对帕金森病进行全面代谢组学分析。
Mol Neurodegener. 2021 Jan 23;16(1):4. doi: 10.1186/s13024-021-00425-8.
10
Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer's Disease.脑淀粉样血管病与阿尔茨海默病患者血浆脂蛋白组成及功能的比较
Biomedicines. 2021 Jan 12;9(1):72. doi: 10.3390/biomedicines9010072.
Zotero 插件