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

doi:10.11817/j.issn.1673-9248.2020.01.008

Abstract

Abstract:

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.

Key words: Cerebral small vessel disease, Apolipoprotein E, Genotype

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.

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References 43

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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

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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