Department of Medical Genetics, University of Lausanne, Switzerland.
J Lipid Res. 2011 Mar;52(3):419-34. doi: 10.1194/jlr.R009761. Epub 2010 Nov 9.
The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.
中枢和周围神经系统髓鞘的完整性受到许多脂质代谢紊乱的影响。到目前为止，这种脆弱性主要归因于形成髓鞘所需的极高水平的脂质合成，以及少突胶质细胞（myelinating glial cells）在脂质合成方面的相对自主性，因为血脑屏障使神经系统免受循环脂质的影响。最近对遗传性脂质代谢紊乱的分析，特别是那些脂质消耗普遍的遗传性脂质代谢紊乱和具有少突胶质细胞特异性脂质代谢紊乱的小鼠模型的分析，为这一问题提供了新的认识。髓鞘的特殊脂质组成、脂质相关髓鞘蛋白的转运以及髓鞘鞘的及时组装的必要性，都导致了观察到的髓鞘对脂质代谢紊乱的脆弱性。此外，外部脂质的摄取也可能在髓鞘膜的形成中发挥作用。除了对基本髓鞘生物学的认识得到提高外，这些数据还为未来旨在保护代谢紊乱中少突胶质细胞完整性的治疗干预提供了基础。
