Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, Milan, Italy.
J Endocrinol Invest. 2013 Jun;36(6):435-43. doi: 10.3275/8941. Epub 2013 Apr 18.
Lipids in the nervous system are represented by cholesterol and phospholipids as constituents of cell membranes and, in particular, of myelin. Therefore, lipids are finely regulated to guarantee physiological functions. In the central nervous system, cholesterol is locally synthesized due to the presence of the blood brain barrier. In the peripheral nervous system cholesterol is either up-taken by lipoproteins and/or produced by de novo biosynthesis. Defects in lipid homeostasis in these tissues lead to structural and functional changes that often result in different pathological conditions depending on the affected pathways (i.e. cholesterol biosynthesis, cholesterol efflux, fatty acid biosynthesis etc.). Alterations in cholesterol metabolism in the central nervous system are linked to several disorders such as Alzheimer's disease, Huntington disease, Parkinson disease, Multiple sclerosis, Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and glioblastoma. In the peripheral nervous system changes in lipid metabolism are associated with the development of peripheral neuropathy that may be caused by metabolic disorders, injuries, therapeutics, and autoimmune diseases. Transcription factors, such as the Liver X receptors (LXR), regulate both cholesterol and fatty acid metabolism in several tissues including the nervous system. In the last few years several studies elucidated the biology of LXR in the nervous system due to the availability of knock-out mice and the development of synthetic ligands. Here, we review a survey of the literature focused on the central and peripheral nervous system and in physiological and pathological settings with particular attention to the roles played by LXR in both districts.
神经系统中的脂质由胆固醇和磷脂组成，是细胞膜的组成部分，特别是髓鞘的组成部分。因此，脂质受到精细的调节以保证生理功能。在中枢神经系统中，由于血脑屏障的存在，胆固醇可以在局部合成。在周围神经系统中，胆固醇可以通过脂蛋白摄取，也可以通过从头合成产生。这些组织中脂质稳态的缺陷会导致结构和功能的改变，这通常会导致不同的病理状况，具体取决于受影响的途径（即胆固醇生物合成、胆固醇外排、脂肪酸生物合成等）。中枢神经系统中胆固醇代谢的改变与几种疾病有关，如阿尔茨海默病、亨廷顿病、帕金森病、多发性硬化症、Smith-Lemli-Opitz 综合征、尼曼-皮克 C 病和神经胶质瘤。在外周神经系统中，脂质代谢的改变与周围神经病变的发展有关，这种病变可能是由代谢紊乱、损伤、治疗和自身免疫性疾病引起的。转录因子，如肝 X 受体 (LXR)，在包括神经系统在内的几种组织中调节胆固醇和脂肪酸代谢。在过去的几年中，由于敲除小鼠的可用性和合成配体的发展，对 LXR 在神经系统中的生物学进行了多项研究，阐明了其生物学功能。在这里，我们综述了文献，重点关注中枢和周围神经系统以及生理和病理环境，特别关注 LXR 在两个区域中所起的作用。
