Zarrouk Amira, Debbabi Meryam, Bezine Maryem, Karym El Mostafa, Badreddine Asmaa, Rouaud Olivier, Moreau Thibault, Cherkaoui-Malki Mustapha, El Ayeb Mohamed, Nasser Boubker, Hammami Mohamed, Lizard Gerard
Department of Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism', University of Bourgogne Franche-Comte / INSERM, Dijon, France.
Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', University of Monastir, Monastir, Tunisia.
Curr Alzheimer Res. 2018 Feb 22;15(4):303-312. doi: 10.2174/1567205014666170505101426.
There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer's disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease.
A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed.
Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage.
There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.
现在有大量证据表明,包括阿尔茨海默病在内的多种神经退行性疾病中脂质代谢受到影响。这些功能障碍导致大脑、脑脊液和血浆中某些脂质水平异常。因此,确定神经退行性疾病中的脂质谱具有重要意义。这种方法有助于识别阿尔茨海默病的脂质生物标志物,也能够识别新的治疗靶点。因此,关注阿尔茨海默病的中枢和外周生物标志物具有重要意义。
对148篇文献进行了综述。基于这些文献,提出了脂质(胆固醇和氧化甾醇、脂肪酸、磷脂)在阿尔茨海默病中的作用。
在引用的148篇关于阿尔茨海默病脂质生物标志物的参考文献中,65篇涉及胆固醇和氧化甾醇,35篇涉及脂肪酸,40篇涉及磷脂。在这些脂质中,其中一些如24S-羟基胆固醇尤其为基因治疗开辟了新的治疗前景。关于极长链脂肪酸的研究结果表明过氧化物酶体功能障碍在阿尔茨海默病中的潜在作用。至于磷脂,它们可能是在前驱期检测该疾病的有趣生物标志物。
现在有几条证据表明脂质在阿尔茨海默病的发病机制中起重要作用,其中一些具有预后和诊断价值。这可能为识别新的治疗靶点、新的有效药物和/或新的治疗方法铺平道路。