Han Xianlin
Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Biochim Biophys Acta. 2010 Aug;1801(8):774-83. doi: 10.1016/j.bbalip.2010.01.010. Epub 2010 Feb 1.
Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a well-developed technology for global lipid analysis, which identifies and quantifies individual lipid molecular species directly from lipid extracts of biological samples. By using this technology, we have revealed three marked changes of lipids in brain samples of subjects with mild cognitive impairment of Alzheimer's disease including sulfatides, ceramides, and plasmalogens. Further studies using MDMS-SL lead us to the identification of the potential biochemical mechanisms responsible for the altered lipids at the disease state, which are thoroughly discussed in this minireview. Specifically, in studies to identify the causes responsible for sulfatide depletion at the mild cognitive impairment stage of Alzheimer's disease, we have found that apolipoprotein E is associated with sulfatide transport and mediates sulfatide homeostasis in the nervous system through lipoprotein metabolism pathways and that alterations in apolipoprotein E-mediated sulfatide trafficking can lead to sulfatide depletion in the brain. Collectively, the results obtained from lipidomic analyses of brain samples provide important insights into the biochemical mechanisms underlying the pathogenesis of Alzheimer's disease.
基于多维质谱的鸟枪法脂质组学(MDMS-SL)是一种成熟的用于全局脂质分析的技术,可直接从生物样品的脂质提取物中鉴定和定量单个脂质分子种类。通过使用该技术,我们揭示了患有阿尔茨海默病轻度认知障碍的受试者脑样本中脂质的三个显著变化,包括硫脂、神经酰胺和缩醛磷脂。使用MDMS-SL的进一步研究使我们能够确定在疾病状态下导致脂质改变的潜在生化机制,本综述对此进行了深入讨论。具体而言,在确定阿尔茨海默病轻度认知障碍阶段硫脂耗竭原因的研究中,我们发现载脂蛋白E与硫脂转运有关,并通过脂蛋白代谢途径介导神经系统中的硫脂稳态,并且载脂蛋白E介导的硫脂运输改变可导致脑中硫脂耗竭。总体而言,从脑样本脂质组学分析中获得的结果为阿尔茨海默病发病机制的生化机制提供了重要见解。