Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer's Disease Risk Factor APOE.
Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer's Disease Risk Factor APOE.
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DOI：
10.3390/cancers12123842
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发表时间：
2020-12-19
期刊：
影响因子：
5.2
通讯作者：
Rebeck GW
中科院分区：
文献类型：
--
作者：
Fernandez HR;Varma A;Flowers SA;Rebeck GW
在过去几年中，对癌症相关认知障碍的病因和潜在治疗方法的研究大大增加。与人类神经心理学和动物行为模型相关的研究取得了进展。这两种类型的研究结果都暗示了遗传风险因子APOE4在癌症相关认知障碍中的作用。APOE4是阿尔茨海默病最强的遗传风险因素，这种跨不同研究方法的融合现在为深入了解这两种疾病的机制提供了一个很好的机会。这篇综述概述了可能导致癌症相关认知障碍的潜在机制，以及APOE基因型如何影响这些机制。癌症相关认知障碍（CRCI）是癌症幸存者维持生活质量的严重障碍。癌症化疗通过几种潜在的机制导致这种情况，包括对血脑屏障的损害，大脑中氧化应激和炎症的增加，以及神经发生受损，每一种都会导致神经元功能障碍。CRCI的遗传易感性是载脂蛋白E基因（APOE）的E4等位基因，这也是阿尔茨海默病最强的遗传风险因素。在正常的大脑中，APOE执行必要的脂质转运功能。APOE4亚型与脂质结合改变、氧化应激和炎症增加、神经祖细胞周转减少和血脑屏障损伤有关。由于化疗也会影响这些过程，APOE4对CRCI的影响具有重要意义。本文综述了APOE基因型在CRCI中可能发挥作用的主要领域。基于APOE生物学的潜在治疗方法可以减轻化疗患者的这些有害认知影响，强调APOE基因型可以帮助制定个性化的癌症治疗方案。
Research into the causes and potential treatments for cancer-related cognitive impairment has increased greatly over the past several years. Advances have been made in studies related to human neuropsychology and animal models of behavior. Findings from both types of studies implicate a role of the genetic risk factor APOE4 in cancer-related cognitive impairment. APOE4 is the strongest genetic risk factor for Alzheimer’s disease, and this convergence across disparate research approaches now provides a great opportunity for insight into mechanisms of both conditions. This review provides an overview of potential mechanisms that could account for aspects of cancer-related cognitive impairment, and how they could be affected by the APOE genotype. Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.
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影响因子：
7.4
作者：
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通讯作者：
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影响因子：
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影响因子：
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通讯作者：
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