载脂蛋白 E 在神经退行性疾病中的信号转导：一种针对载脂蛋白 E 编码和非编码变异体的疾病干预的综合方法。

APOE signaling in neurodegenerative diseases: an integrative approach targeting APOE coding and noncoding variants for disease intervention.

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, Hong Kong University of Science and Technology Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, 518057 Shenzhen, Guangdong, China.

出版信息

Curr Opin Neurobiol. 2021 Aug;69:58-67. doi: 10.1016/j.conb.2021.02.001. Epub 2021 Feb 26.

DOI:10.1016/j.conb.2021.02.001

PMID:33647674

Abstract

APOE (apolipoprotein E) is a key regulator of lipid metabolism and a leading genetic risk factor for Alzheimer's disease. While APOE participates in multiple biological pathways, its roles in diseases are largely due to the mutant protein encoded by APOE-ε4. However, emerging evidence suggests that some noncoding Alzheimer's disease risk variants residing in APOE and its nearby regions exert APOE-ε4-independent risks and modify APOE gene expression. Moreover, intervention strategies targeting APOE are being explored. In this review, we summarize the literature on the genetic risks and roles of APOE in biological systems. Moreover, we propose an integrative approach to evaluate disease risk and tailor interventions to aid research on APOE-associated diseases.

摘要

载脂蛋白 E（APOE）是脂质代谢的关键调节剂，也是阿尔茨海默病的主要遗传风险因素。虽然 APOE 参与多种生物学途径，但它在疾病中的作用主要归因于 APOE-ε4 编码的突变蛋白。然而，新出现的证据表明，APOE 及其附近区域中一些非编码的阿尔茨海默病风险变异体发挥着 APOE-ε4 独立的风险，并修饰 APOE 基因表达。此外，针对 APOE 的干预策略也正在探索中。在这篇综述中，我们总结了 APOE 在生物系统中的遗传风险和作用的文献。此外，我们提出了一种综合方法来评估疾病风险，并调整干预措施，以帮助研究与 APOE 相关的疾病。