Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.
Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.
复制标题
重复扩张疾病中的基因环境相互作用：环境诱导的重复不稳定的机制。
DOI：
10.3390/biomedicines11020515
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发表时间：
2023-02-10
期刊：
影响因子：
4.7
通讯作者：
Pearson, Brandon L. L.
中科院分区：
文献类型：
--
作者：
Calluori, Stephanie;Stark, Rebecca;Pearson, Brandon L. L.
关键词：
短串联重复 (STR) 是 1-6 个碱基对的单位，以串联重复形式出现，形成重复序列。 STR 表现出重复不稳定性，这会产生重复区的扩张或收缩。超过 50 种疾病主要影响中枢神经系统和肌肉，其特点是重复不稳定。较长的重复束通常与发病年龄较早和疾病严重程度增加有关。环境暴露被怀疑在重复扩张疾病的发病机制中发挥作用。在这里，我们回顾了重复扩张疾病中环境引起的重复不稳定性机制的当前知识。目前的证据表明，环境因素通过 DNA 损伤和 DNA 修复途径的诱导来调节重复不稳定性，并具有不同的重复扩张和收缩机制。特别值得注意的是，氧化应激是环境引起的重复不稳定的关键介质。初步证据表明表观遗传修饰是环境引起的重复不稳定性的潜在介质。未来的研究结合了一系列环境暴露、新的人类群体和改进的模型系统，并继续关注细胞类型、组织和关键窗口，将有助于识别环境引起的重复不稳定性的机制。识别重复不稳定的环境调节剂及其作用机制将为预防、治疗和公共卫生措施提供信息。
Short tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are characterized by repeat instability. Longer repeat tracts are typically associated with earlier age of onset and increased disease severity. Environmental exposures are suspected to play a role in the pathogenesis of repeat expansion diseases. Here, we review the current knowledge of mechanisms of environmentally induced repeat instability in repeat expansion diseases. The current evidence demonstrates that environmental factors modulate repeat instability via DNA damage and induction of DNA repair pathways, with distinct mechanisms for repeat expansion and contraction. Of particular note, oxidative stress is a key mediator of environmentally induced repeat instability. The preliminary evidence suggests epigenetic modifications as potential mediators of environmentally induced repeat instability. Future research incorporating an array of environmental exposures, new human cohorts, and improved model systems, with a continued focus on cell-types, tissues, and critical windows, will aid in identifying mechanisms of environmentally induced repeat instability. Identifying environmental modulators of repeat instability and their mechanisms of action will inform preventions, therapies, and public health measures.
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影响因子：
3.5
作者：
Møllersen L;Rowe AD;Illuzzi JL;Hildrestrand GA;Gerhold KJ;Tveterås L;Bjølgerud A;Wilson DM 3rd;Bjørås M;Klungland A
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作者：
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通讯作者：
KOLODNER, R
影响因子：
1.9
作者：
Aziz, N. Ahmad;van Belzen, Martine J.;Roos, Raymund A. C.
通讯作者：
Roos, Raymund A. C.