脂筏、胆固醇与大脑。
Lipid rafts, cholesterol, and the brain.
作者信息
Korade Zeljka, Kenworthy Anne K
机构信息
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
出版信息
Neuropharmacology. 2008 Dec;55(8):1265-73. doi: 10.1016/j.neuropharm.2008.02.019. Epub 2008 Mar 14.
Abstract
Lipid rafts are specialized membrane microdomains that serve as organizing centers for assembly of signaling molecules, influence membrane fluidity and trafficking of membrane proteins, and regulate different cellular processes such as neurotransmission and receptor trafficking. In this article, we provide an overview of current methods for studying lipid rafts and models for how lipid rafts might form and function. Next, we propose a potential mechanism for regulating lipid rafts in the brain via local control of cholesterol biosynthesis by neurotrophins and their receptors. Finally, we discuss evidence that altered cholesterol metabolism and/or lipid rafts play a critical role in the pathophysiology of multiple CNS disorders, including Smith-Lemli-Opitz syndrome, Huntington's, Alzheimer's, and Niemann-Pick Type C diseases.
摘要
脂筏是特殊的膜微区，作为信号分子组装的组织中心，影响膜流动性和膜蛋白运输，并调节不同的细胞过程，如神经传递和受体运输。在本文中，我们概述了目前研究脂筏的方法以及脂筏可能形成和发挥功能的模型。接下来，我们提出了一种潜在机制，通过神经营养因子及其受体对胆固醇生物合成的局部控制来调节大脑中的脂筏。最后，我们讨论了胆固醇代谢改变和/或脂筏在多种中枢神经系统疾病（包括史密斯-马吉利-奥皮茨综合征、亨廷顿舞蹈症、阿尔茨海默病和尼曼-匹克C型病）的病理生理学中起关键作用的证据。
相似文献
1
Lipid rafts, cholesterol, and the brain.脂筏、胆固醇与大脑。
Neuropharmacology. 2008 Dec;55(8):1265-73. doi: 10.1016/j.neuropharm.2008.02.019. Epub 2008 Mar 14.
2
Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts.胆固醇在尼曼-匹克 C 型（NPC）模型细胞中的积累导致 APP 定位向脂筏转移。
Biochem Biophys Res Commun. 2010 Mar 12;393(3):404-9. doi: 10.1016/j.bbrc.2010.02.007. Epub 2010 Feb 6.
3
Precholesterol sterols accumulate in lipid rafts of patients with Smith-Lemli-Opitz syndrome and X-linked dominant chondrodysplasia punctata.前胆固醇甾醇在患有史密斯-勒米-奥皮茨综合征和X连锁显性点状软骨发育不良的患者的脂筏中积累。
Pediatr Dev Pathol. 2008 Mar-Apr;11(2):128-32. doi: 10.2350/06-10-0179.1. Epub 2007 Mar 22.
4
Formation of 7-dehydrocholesterol-containing membrane rafts in vitro and in vivo, with relevance to the Smith-Lemli-Opitz syndrome.体外和体内含7-脱氢胆固醇膜筏的形成及其与Smith-Lemli-Opitz综合征的相关性
J Lipid Res. 2004 Feb;45(2):347-55. doi: 10.1194/jlr.M300232-JLR200. Epub 2003 Nov 1.
5
Different Trafficking Phenotypes of Niemann-Pick C1 Gene Mutations Correlate with Various Alterations in Lipid Storage, Membrane Composition and Miglustat Amenability.尼曼-匹克 C1 基因突变的不同转运表型与脂质储存、膜组成和米格列醇适应性的各种改变相关。
Int J Mol Sci. 2020 Mar 19;21(6):2101. doi: 10.3390/ijms21062101.
6
7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome.7-脱氢胆固醇在 Smith-Lemli-Opitz 综合征小鼠模型中有效支持 Ret 信号通路。
Sci Rep. 2016 Jun 23;6:28534. doi: 10.1038/srep28534.
7
[Cholesterol and lipid rafts in the biological membranes. Role in the release, reception and ion channel functions].[生物膜中的胆固醇与脂筏。在释放、接收及离子通道功能中的作用]
Usp Fiziol Nauk. 2013 Jan-Mar;44(1):17-38.
8
Defective insulin receptor activation and altered lipid rafts in Niemann-Pick type C disease hepatocytes.尼曼-匹克C型病肝细胞中胰岛素受体激活缺陷与脂筏改变。
Biochem J. 2005 Nov 1;391(Pt 3):465-72. doi: 10.1042/BJ20050460.
9
Oxysterols: Influence on plasma membrane rafts microdomains and development of ocular diseases.氧化甾醇：对质膜脂筏微结构域及眼部疾病发展的影响
Steroids. 2015 Jul;99(Pt B):259-65. doi: 10.1016/j.steroids.2015.02.004. Epub 2015 Feb 12.
10
Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases.脂质筏与神经退行性变：在生理衰老和神经退行性疾病中的结构和功能作用。
J Lipid Res. 2020 May;61(5):636-654. doi: 10.1194/jlr.TR119000427. Epub 2019 Dec 23.
引用本文的文献
1
Role of PDGFRα-mediated signalling in anoikis resistance in glioblastoma: in vitro study.血小板衍生生长因子受体α介导的信号传导在胶质母细胞瘤失巢凋亡抗性中的作用：体外研究
In Vitro Cell Dev Biol Anim. 2025 Jul 21. doi: 10.1007/s11626-025-01075-6.
2
Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.神经退行性疾病中的脂质代谢与他汀类药物治疗：内分泌视角
Metabolites. 2025 Apr 18;15(4):282. doi: 10.3390/metabo15040282.
3
Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder.神经节苷脂与胆固醇：自闭症谱系障碍中神经元膜框架的双重调节因子
Int J Mol Sci. 2025 Feb 4;26(3):1322. doi: 10.3390/ijms26031322.
4
Nanoscale drug formulations for the treatment of Alzheimer's disease progression.用于治疗阿尔茨海默病进展的纳米级药物制剂。
RSC Adv. 2025 Feb 7;15(6):4031-4078. doi: 10.1039/d4ra08128e. eCollection 2025 Feb 6.
5
Cholesterol promotes mRNA expression in CD4 effector/memory cells by SGK1 activation.胆固醇通过 SGK1 激活促进 CD4 效应/记忆细胞中的 mRNA 表达。
Life Sci Alliance. 2024 Oct 4;7(12). doi: 10.26508/lsa.202402890. Print 2024 Dec.
6
Cholesterol-Dependent Serotonin Insertion Controlled by Gangliosides in Model Lipid Membranes.胆固醇依赖的血清素插入由模型脂膜中的神经节苷脂控制。
Int J Mol Sci. 2024 Sep 23;25(18):10194. doi: 10.3390/ijms251810194.
7
Short-Term Treatment of Melatonin Improves the Expression of Cell Adhesion Molecules in the Testis of the Mouse Cryptorchidism Model.短期褪黑素治疗可改善隐睾症模型小鼠睾丸细胞黏附分子的表达。
J Histochem Cytochem. 2024 Oct;72(10):623-640. doi: 10.1369/00221554241279505. Epub 2024 Sep 20.
8
Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts.胆固醇介导的水通道蛋白 0 阵列的结构和动力学及其对脂筏的影响。
Elife. 2024 Sep 2;12:RP90851. doi: 10.7554/eLife.90851.
9
Cholesterol imbalance and neurotransmission defects in neurodegeneration.胆固醇失衡与神经退行性变中的神经传递缺陷。
Exp Mol Med. 2024 Aug;56(8):1685-1690. doi: 10.1038/s12276-024-01273-4. Epub 2024 Aug 1.
10
Lipid Rafts: The Maestros of Normal Brain Development.脂质筏：正常大脑发育的指挥家。
Biomolecules. 2024 Mar 18;14(3):362. doi: 10.3390/biom14030362.
本文引用的文献
1
Dynamic clustered distribution of hemagglutinin resolved at 40 nm in living cell membranes discriminates between raft theories.在活细胞膜中以40纳米分辨率解析的血凝素动态簇状分布区分了不同的脂筏理论。
Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17370-5. doi: 10.1073/pnas.0708066104. Epub 2007 Oct 24.
2
Structural determinants for partitioning of lipids and proteins between coexisting fluid phases in giant plasma membrane vesicles.巨型质膜囊泡中共存液相之间脂质和蛋白质分配的结构决定因素。
Biochim Biophys Acta. 2008 Jan;1778(1):20-32. doi: 10.1016/j.bbamem.2007.08.028. Epub 2007 Sep 12.
3
Brain-derived neurotrophic factor regulates cholesterol metabolism for synapse development.脑源性神经营养因子调节胆固醇代谢以促进突触发育。
J Neurosci. 2007 Jun 13;27(24):6417-27. doi: 10.1523/JNEUROSCI.0690-07.2007.
4
Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2.动态募集磷脂酶Cγ至瞬时固定的糖基磷脂酰肌醇锚定受体簇诱导IP3-Ca2+信号传导：单分子追踪研究2
J Cell Biol. 2007 May 21;177(4):731-42. doi: 10.1083/jcb.200609175.
5
GPI-anchored receptor clusters transiently recruit Lyn and G alpha for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1.糖基磷脂酰肌醇（GPI）锚定受体簇短暂招募Lyn和Gα，以实现临时簇固定和Lyn激活：单分子追踪研究1 。
J Cell Biol. 2007 May 21;177(4):717-30. doi: 10.1083/jcb.200609174.
6
Differential effects of cholesterol and 7-dehydrocholesterol on the ligand binding activity of the hippocampal serotonin(1A) receptor: implications in SLOS.胆固醇和7-脱氢胆固醇对海马5-羟色胺（1A）受体配体结合活性的差异影响：对Smith-Lemli-Opitz综合征的启示
Biochem Biophys Res Commun. 2007 Jun 29;358(2):495-9. doi: 10.1016/j.bbrc.2007.04.135. Epub 2007 Apr 30.
7
Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies.利用环糊精调控质膜胆固醇含量：证据、误解与控制策略
Biochim Biophys Acta. 2007 Jun;1768(6):1311-24. doi: 10.1016/j.bbamem.2007.03.026. Epub 2007 Apr 6.
8
Developmental changes in the association of NMDA receptors with lipid rafts.N-甲基-D-天冬氨酸受体与脂筏关联的发育变化
J Neurosci Res. 2007 Jul;85(9):1876-83. doi: 10.1002/jnr.21336.
9
Role of sterol type on lateral pressure profiles of lipid membranes affecting membrane protein functionality: Comparison between cholesterol, desmosterol, 7-dehydrocholesterol and ketosterol.甾醇类型对影响膜蛋白功能的脂膜侧向压力分布的作用：胆固醇、羊毛甾醇、7-脱氢胆固醇和酮甾醇之间的比较
J Struct Biol. 2007 Aug;159(2):311-23. doi: 10.1016/j.jsb.2007.01.012. Epub 2007 Feb 1.
10
Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles.巨质膜囊泡中蛋白质和脂质的大规模液/液相分离
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3165-70. doi: 10.1073/pnas.0611357104. Epub 2007 Feb 21.
Zotero 插件