Priority Organization for Innovation and Excellence, Kumamoto University, Honjo, Japan.
Biol Pharm Bull. 2011;34(4):453-61. doi: 10.1248/bpb.34.453.
Lipoproteins in the central nervous system (CNS) are not incorporated from the blood but are formed mainly by glial cells within the CNS. In addition, cholesterol in the CNS is synthesized endogenously because the blood-brain barrier segregates the CNS from the peripheral circulation. Apolipoprotein (apo) E is a major apo in the CNS. In normal condition, apo E is secreted from glia, mainly from astrocytes, and forms cholesterol-rich lipoproteins by ATP-binding cassette transporters. Subsequently, apo E-containing glial lipoproteins supply cholesterol and other components to neurons via a receptor-mediated process. Recent findings demonstrated that receptors of the low density lipoprotein (LDL) receptor family not only internalize lipoproteins into the cells but also, like signaling receptors, transduce signals upon binding the ligands. In this review, the regulation of lipid homeostasis will be discussed as well as roles of lipoproteins and functions of receptors of LDL receptor family in the CNS. Furthermore, the relation between lipid metabolism and Alzheimer's disease (AD) is discussed.
中枢神经系统(CNS)中的脂蛋白不是从血液中摄取的,而是主要由 CNS 中的神经胶质细胞形成的。此外,由于血脑屏障将 CNS 与外周循环分隔开,CNS 中的胆固醇是内源性合成的。载脂蛋白(apo)E 是 CNS 中的主要 apo。在正常情况下,apo E 由神经胶质细胞分泌,主要由星形胶质细胞分泌,并通过 ATP 结合盒转运蛋白形成富含胆固醇的脂蛋白。随后,载脂蛋白 E 包含的神经胶质脂蛋白通过受体介导的过程将胆固醇和其他成分供应给神经元。最近的研究结果表明,低密度脂蛋白(LDL)受体家族的受体不仅将脂蛋白内化到细胞内,而且像信号受体一样,在结合配体后传递信号。在这篇综述中,将讨论脂质稳态的调节以及脂蛋白和 LDL 受体家族受体在 CNS 中的作用。此外,还讨论了脂质代谢与阿尔茨海默病(AD)之间的关系。