APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer's.
APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer's.
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DOI：
10.3390/ijms22031244
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发表时间：
2021-01-27
影响因子：
5.6
通讯作者：
Chiba-Falek O
中科院分区：
文献类型：
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作者：
Yang A;Kantor B;Chiba-Falek O
阿尔茨海默病 (AD) 的医疗需求尚未得到满足。围绕淀粉样蛋白级联假说的共识一直指导临床前和临床研究主要集中于针对β-淀粉样蛋白治疗AD。然而，绝大多数临床试验屡屡失败，促使迫切需要重新关注其他靶点，并将 AD 药物开发范式转向精准医疗。其中一个新兴目标是载脂蛋白 E (APOE)，它在近 30 年前被确定为晚发性阿尔茨海默氏病 (LOAD) 最强、最可复制的遗传风险因素之一。对 APOE 作为新的治疗罪魁祸首的探索已经产生了一些非常令人鼓舞的结果，证明该蛋白质在 LOAD 疗法中具有前景。在这里，我们回顾了基于反义寡核苷酸、单克隆抗体和基因/碱基编辑等最先进技术的靶向 APOE 的策略。我们讨论了这些举措在推动新型精准医学疗法 LOAD 开发方面的潜力。
Alzheimer’s disease (AD) has a critical unmet medical need. The consensus around the amyloid cascade hypothesis has been guiding pre-clinical and clinical research to focus mainly on targeting beta-amyloid for treating AD. Nevertheless, the vast majority of the clinical trials have repeatedly failed, prompting the urgent need to refocus on other targets and shifting the paradigm of AD drug development towards precision medicine. One such emerging target is apolipoprotein E (APOE), identified nearly 30 years ago as one of the strongest and most reproduceable genetic risk factor for late-onset Alzheimer’s disease (LOAD). An exploration of APOE as a new therapeutic culprit has produced some very encouraging results, proving that the protein holds promise in the context of LOAD therapies. Here, we review the strategies to target APOE based on state-of-the-art technologies such as antisense oligonucleotides, monoclonal antibodies, and gene/base editing. We discuss the potential of these initiatives in advancing the development of novel precision medicine therapies to LOAD.
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APOE 位点遗传变异的功能分析表明区域增强子参与 TOMM40 和 APOE 的调节。
影响因子：
3.5
作者：
通讯作者：
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DOI：
10.1523/jneurosci.0033-12.2012
发表时间：
2012-04-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Huang Y
影响因子：
30.8
作者：
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通讯作者：
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影响因子：
4.2
作者：
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通讯作者：
Emre M
DOI：
10.1016/j.omtn.2018.03.007
发表时间：
2018-06-01
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
György B;Lööv C;Zaborowski MP;Takeda S;Kleinstiver BP;Commins C;Kastanenka K;Mu D;Volak A;Giedraitis V;Lannfelt L;Maguire CA;Joung JK;Hyman BT;Breakefield XO;Ingelsson M
通讯作者：
Ingelsson M