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中华脑血管病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (01) : 40 -46. doi: 10.11817/j.issn.1673-9248.2020.01.008

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专家论坛

载脂蛋白E基因及相关蛋白在脑小血管病中的作用研究进展
陈慧敏1, 王伊龙1,()   
  1. 1. 100070 首都医科大学附属北京天坛医院神经病学中心 国家神经系统疾病临床医学研究中心 北京脑重大疾病研究院脑卒中研究所
  • 收稿日期:2019-12-26 出版日期:2020-02-01
  • 通信作者: 王伊龙
  • 基金资助:
    国家自然科学基金委员会杰出青年科学基金项目(81825007); 北京高校卓越青年科学家计划项目(BJJWZYJH01201910025030); 科技部“十三五”国家重点研发计划“症状性颅内外大动脉狭窄复发进展预测模型与干预策略研究”(2017YFC1307900); 北京市科学技术委员会北京市科技计划“动脉粥样硬化性颅内动脉狭窄的他汀药物治疗研究”(D171100003017001); 北京市科学技术委员会北京市优秀人才培养资助-青年拔尖团队(2016000021223TD03); 青年北京学者

Update on association among cerebral small vessel disease, APOE genotype and related protein

Huimin Chen1, Yilong Wang1,()   

  1. 1. Department of Neurology, Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China
  • Received:2019-12-26 Published:2020-02-01
  • Corresponding author: Yilong Wang
  • About author:
    Corresponding author: Wang Yilong, Email:
引用本文:

陈慧敏, 王伊龙. 载脂蛋白E基因及相关蛋白在脑小血管病中的作用研究进展[J]. 中华脑血管病杂志(电子版), 2020, 14(01): 40-46.

Huimin Chen, Yilong Wang. Update on association among cerebral small vessel disease, APOE genotype and related protein[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2020, 14(01): 40-46.

载脂蛋白E基因多态性可能与脑小血管病相关。载脂蛋白E基因多态性可能通过Aβ毒性作用和相关通路、脂蛋白代谢紊乱、血管神经单元破坏等机制引起脑小血管病相关影像学改变(脑白质病变、腔隙、微出血、血管周围间隙、脑萎缩)。载脂蛋白E基因多态性可能介导脑小血管病、阿尔茨海默病、缺血性卒中表型上的重叠,也可能介导脑小血管病影像表型的异质性。载脂蛋白E基因多态性及其相关蛋白能否作为脑小血管病治疗靶点,有待进一步研究。

Apolipoprotein E gene polymorphism may be associated with cerebral small vessel disease. Apolipoprotein E gene polymorphism may cause cerebral small vessel pathology (white matter lesions, lacunae, microbleeding, perivascular spaces, brain atrophy), through Aβ toxicity and Aβ related pathways, lipoprotein dysmetabolism, or destruction of neurovascular unit. Apolipoprotein E gene polymorphism may mediate the phenotypes overlap among cerebral small vessel disease, Alzheimer's disease and ischemic stroke, and may also mediate the heterogeneity of cerebral small vessel disease. Whether apolipoprotein E gene polymorphisms and related proteins can be used as therapeutic targets for cerebral small vessel disease remains to be investigated.

表1 针对载脂蛋白E基因多态性及其相关蛋白的潜在治疗靶点
目的 方法 逻辑 举例
控制载脂蛋白E含量 调节载脂蛋白E含量

刺激Aβ清除

维持脂质稳态

增强突触功能

腺相关病毒介导的基因传递,载脂蛋白E基因沉默技术,维甲酸X受体激动剂,肝X受体激动剂
载脂蛋白E模拟肽

减少炎症

减少细胞毒性

增加载脂蛋白E相关功能

包含载脂蛋白E受体结合区的肽
改变载脂蛋白E功能 增加载脂蛋白E的脂质化 减少Aβ沉积
阻止载脂蛋白E和Aβ的相互作用 阻碍Aβ聚集 载脂蛋白E特异抗体、Aβ12-28P,载脂蛋白E多肽
阻止载脂蛋白E的聚集

减少Aβ聚集

阻止载脂蛋白E ε4相关毒性作用

抗载脂蛋白E抗体和小分子
使载脂蛋白E ε4转变为载脂蛋白E ε3

增加载脂蛋白E的保护作用

阻碍载脂蛋白E ε4功能域的结合作用

降低载脂蛋白E ε4的细胞毒性作用

CRISPR/Cas9,载脂蛋白E结构纠正药物
恢复载脂蛋白E蛋白功能

增加载脂蛋白E蛋白的保护作用

减少炎性反应

载脂蛋白E模拟肽
阻止载脂蛋白E蛋白异常分解

减少tau病理变化

减少细胞毒性作用

载脂蛋白E蛋白溶酶抑制剂
受体修饰 恢复载脂蛋白E蛋白受体功能 促进胆固醇转运加强Aβ清除增加信号传导和突触可塑性 小分子
调节载脂蛋白E蛋白和受体转运 恢载脂蛋白E蛋白和受体功能 小分子
增加低密度脂蛋白受体相关蛋白-1和低密度脂蛋白受体 加强Aβ清除胆固醇转运和突触可塑性 小分子
增加低密度脂蛋白受体相关蛋白-2和极低密度脂蛋白受体 增加信号传导和突触可塑性 小分子
靶向胰岛素 控制胰岛素通路

改善脑内糖代谢

诱导高酮血症,改善脑糖依赖性和线粒体功能

酮剂(酮体),调酮饮食
其他 改善血管神经单元完整性 促进Aβ清除抑制载脂蛋白E ε4协助的血脑屏障破坏 环胞素A
载脂蛋白E基因型和免疫治疗 协助增强Aβ相关的临床治疗和其他治疗 Aβ免疫治疗
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