Montani Laura
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, Zürich, CH-8093, Switzerland.
Semin Cell Dev Biol. 2021 Apr;112:114-122. doi: 10.1016/j.semcdb.2020.07.016. Epub 2020 Sep 8.
Oligodendrocytes enwrap central nervous system axons with myelin, a lipid enriched highly organized multi-layer membrane structure that allows for fast long-distance saltatory conduction of neuronal impulses. Myelin has an extremely high lipid content (∼80 % of its dry weight) and a peculiar lipid composition, with a 2:2:1 cholesterol:phospholipid:glycolipid ratio. Inherited neurodegenerative diseases of the lipids (caused by mutations in lipogenic enzymes) often present oligodendrocyte and/or myelin defects which contribute to the overall disease pathophysiology. These phenomena triggered an increasing number of studies over the functions lipid exert to shape and maintain myelin, and brought to the finding that lipids are more than only structural building blocks. They act as signaling molecules to drive proliferation and differentiation of oligodendrocyte progenitor cells, as well as proliferation of premyelinating oligodendrocytes, and their maturation into myelinating ones. Here, we summarize key findings in these areas, while presenting the main related human diseases. Despite many advances in the field, various questions remain open which we briefly discuss. This article is part of a special issue entitled "Role of Lipids in CNS Cell Physiology and Pathology".
少突胶质细胞用髓鞘包裹中枢神经系统轴突,髓鞘是一种富含脂质的高度有序的多层膜结构,可实现神经元冲动的快速长距离跳跃传导。髓鞘具有极高的脂质含量(约占其干重的80%)和独特的脂质组成,胆固醇:磷脂:糖脂的比例为2:2:1。遗传性脂质神经退行性疾病(由脂肪生成酶的突变引起)常出现少突胶质细胞和/或髓鞘缺陷,这对整体疾病病理生理学有影响。这些现象引发了越来越多关于脂质在塑造和维持髓鞘方面功能的研究,并发现脂质不仅仅是结构组成部分。它们作为信号分子驱动少突胶质前体细胞的增殖和分化,以及未成熟少突胶质细胞的增殖,并使其成熟为髓鞘形成细胞。在这里,我们总结这些领域的关键发现,同时介绍主要的相关人类疾病。尽管该领域取得了许多进展,但仍存在各种未解决的问题,我们将简要讨论。本文是名为“脂质在中枢神经系统细胞生理学和病理学中的作用”的特刊的一部分。