ApoE Lipidation as a Therapeutic Target in Alzheimer's Disease.
ApoE Lipidation as a Therapeutic Target in Alzheimer's Disease.
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DOI：
10.3390/ijms21176336
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Rebeck GW
中科院分区：
文献类型：
--
作者：
Lanfranco MF;Ng CA;Rebeck GW
载脂蛋白E （APOE）是大脑中主要的胆固醇载体，影响各种正常细胞过程，包括神经元生长、膜修复和重塑、突触发生、β淀粉样蛋白（Aβ）的清除和降解以及神经炎症。在人类中，APOE基因有三种常见的等位基因变体，分别是E2、E3和E4。APOE4被认为是阿尔茨海默病（AD）最强的遗传风险因素，而APOE2具有神经保护作用。为了发挥其正常功能，载脂蛋白e必须分泌并适当脂化，这一过程受到载脂蛋白e同型体相关结构差异的影响。在这里，我们强调脂化apoE的重要性，以及针对apoE脂化的治疗方法有可能纠正或预防神经变性。许多这些方法已经通过不同的细胞和动物模型得到了验证。总之，改善apoE脂化状态以改善apoE相关的中枢神经系统损伤具有很大的潜力。
Apolipoprotein E (APOE) is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance and degradation of amyloid β (Aβ) and neuroinflammation. In humans, the APOE gene has three common allelic variants, termed E2, E3, and E4. APOE4 is considered the strongest genetic risk factor for Alzheimer’s disease (AD), whereas APOE2 is neuroprotective. To perform its normal functions, apoE must be secreted and properly lipidated, a process influenced by the structural differences associated with apoE isoforms. Here we highlight the importance of lipidated apoE as well as the APOE-lipidation targeted therapeutic approaches that have the potential to correct or prevent neurodegeneration. Many of these approaches have been validated using diverse cellular and animal models. Overall, there is great potential to improve the lipidated state of apoE with the goal of ameliorating APOE-associated central nervous system impairments.
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影响因子：
4.8
作者：
Chen, Hung-Kai;Ji, Zhong-Sheng;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
影响因子：
4.2
作者：
DeMattos, RB;Brendza, RP;Holtzman, DM
通讯作者：
Holtzman, DM
影响因子：
5.3
作者：
Boehm-Cagan, Anat;Michaelson, Daniel M.
通讯作者：
Michaelson, Daniel M.
影响因子：
4.8
作者：
Chen, Hung-Kai;Liu, Zhaoping;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
DOI：
10.1073/pnas.0812697106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Agosta, Federica;Vossel, Keith A.;Gorno-Tempini, Maria Luisa
通讯作者：
Gorno-Tempini, Maria Luisa