Marangon Davide, Boccazzi Marta, Lecca Davide, Fumagalli Marta
Department of Phamacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, 9-20133 Milan, Italy.
J Clin Med. 2020 Feb 8;9(2):470. doi: 10.3390/jcm9020470.
Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.
髓磷脂是一种重要结构，可保护轴突，为神经元提供代谢支持并实现快速神经传导。多种神经疾病，如多发性硬化症，其特征为髓磷脂损伤，这会导致严重的功能障碍。髓磷脂修复需要成年少突胶质前体细胞（OPCs）及时募集到损伤部位，并分化成熟为形成髓鞘的少突胶质细胞。因此，OPCs在形态、功能以及与其他细胞和细胞外环境的相互作用方面会发生深刻变化，这就需要重新组织其脂质代谢和膜组成，而这与其他质膜有很大不同。尽管对少突胶质细胞生物学以及OPC介导的再生机制的了解不断增加，但确定促进髓鞘再生的策略仍然是一项挑战。在此，我们描述了少突胶质细胞中脂质代谢改变如何影响脱髓鞘的发病机制，并且我们表明几种先前未知具有促进髓鞘再生潜力的FDA批准药物确实作用于胆固醇和脂质生物合成途径。由于髓磷脂脂质与轴突之间的相互作用由细胞外基质（ECM）严格协调，我们还讨论了不同ECM成分的作用，并报告了关于能够促进内源性髓鞘再生的新型ECM调节剂的最新研究结果。
