MicroRNA silencing: A promising therapy for Alzheimer's disease.
MicroRNA silencing: A promising therapy for Alzheimer's disease.
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DOI：
10.46439/neuroscience.1.004
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发表时间：
2020
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影响因子：
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通讯作者：
Chauhan, Neelima B
中科院分区：
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作者：
Chauhan, Neelima B
阿尔茨海默病 (AD) 是一种全球健康危机，目前困扰着约 600 万美国人（以及全世界约 4000 万人）。如果没有发现突破性的疾病缓解疗法，到本世纪中叶，患有 AD 的美国人（以及全世界约 1.52 亿人）的数字将达到惊人的水平。目前，尚无预防、阻止或治愈该疾病的治疗方法。对大脑基因表达模式的多项独立研究表明，在 AD 中，大约 1/3 的基因上调，而其余 2/3 的基因下调。在这方面，专注于 antagomiR 介导的“上调”microRNA（miR）沉默的 AD 疗法可能更可行，因为 AD 中上调的 miR 随着疾病进展而持续增加，而 agomiR 介导的下调 miR 的过度表达在 AD 脑病理条件下存在不可预测的减少和相对较短的 1-3 小时寿命。迄今为止的研究表明，AD 中大多数上调的致病基因都是由促炎性 microRNA (miR) 调节的。鉴于慢性神经炎症优先触发 AD 样神经变性以及 AD 的多因素性质，使用反义 microRNA 沉默炎症特异性 micro-RNA 可能是预防、阻止或治愈 AD 的有效辅助治疗策略。
Alzheimer’s disease (AD) is a global health crisis currently afflicting ~6 million Americans (and ~40 million people worldwide). By the middle of the century, these numbers will stagger by ~16 million Americans (and ~152 million people worldwide) suffering from AD, if breakthrough disease-modifying treatments are not discovered. Currently, there are no treatments to prevent, halt or cure the disease. Multiple independent studies on brain gene expression patterns have indicated that in AD about 1/3rd of the genes are upregulated while the rest 2/3rd of the genes are downregulated. In that regard, AD therapeutics focused on antagomiR-mediated silencing of“upregulated”microRNAs (miRs) may be more feasible since upregulated miRs in AD continue to increase with the disease progression, as opposed to agomiR-mediated overexpression of down-regulated miRs with unpredictable reduced presence and relative short-life of 1–3h under pathological conditions in AD brain. Studies reported thus far indicate that most of the upregulated pathogenic genes in AD are regulated by pro-inflammatory microRNAs (miRs). Given the precedence of chronic neuroinflammation in triggering AD-like neurodegeneration and multifactorial nature of AD, silencing inflammation-specific micro-RNAs using antisense-microRNAs may be an effective adjuvant therapeutic strategy to prevent, halt or cure AD.