Korade Zeljka, Kenworthy Anne K
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Neuropharmacology. 2008 Dec;55(8):1265-73. doi: 10.1016/j.neuropharm.2008.02.019. Epub 2008 Mar 14.
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.
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。
