Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Tahir Foundation Building, MD1, 16-03-H, 12 Science Drive 2, Singapore, 117549, Singapore.
Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Transl Neurodegener. 2022 Nov 7;11(1):48. doi: 10.1186/s40035-022-00322-0.
Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations in SPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circulation is associated with ALS. Here, we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis. Among the different lipids, accumulation of ceramides, arachidonic acid, and lysophosphatidylcholine is commonly emerging as detrimental to motor neurons. We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
脂质在水中的溶解度低，在非极性溶剂中的溶解度高，可以分为脂肪酸、甘油磷脂、甘油磷酸脂、鞘脂和固醇。脂质不仅调节生物膜的完整性和流动性，而且作为信号传导的储能和生物活性分子。在肌萎缩侧索硬化症（ALS）中，即在一种导致瘫痪和致命的运动神经元疾病中，已经确定了脂肪生成途径中 SPTLC1（丝氨酸棕榈酰转移酶长链亚基 1）基因的因果突变。此外，中枢神经系统和循环中的脂质代谢紊乱与 ALS 有关。在这里，我们旨在描绘不同脂质类别的多种作用，并了解脂质代谢紊乱如何可能导致 ALS 的发病机制。在不同的脂质中，神经酰胺、花生四烯酸和溶血磷脂酰胆碱的积累通常被认为对运动神经元有害。最后，我们探索通过减少这些有毒脂质来治疗 ALS 的潜在疗法。
Zotero 插件
