Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases.
Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases.
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DOI：
10.1007/s00109-012-0962-4
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发表时间：
2012-12
影响因子：
4.7
通讯作者：
Moskalev, Alexey
中科院分区：
文献类型：
--
作者：
Zhavoronkov, Alex;Smit-McBride, Zeljka;Guinan, Kieran J.;Litovchenko, Maria;Moskalev, Alexey
近年来，对衰老的遗传成分的科学认识有所增加，一些基因被确定为在衰老过程中发挥作用，并可能影响寿命。特别是，基因编码的真核生物核纤层的组成部分已越来越好的特点，部分原因是它们在与年龄有关的疾病的临床意义。本文综述了一个这样的基因，它编码核纤层蛋白A，核纤层的关键组成部分。这种基因的遗传变异可以引起致命的早发性疾病，称为核纤层蛋白病。在这里，我们分析了文献，并进行计算分析核纤层蛋白A信号和细胞内的相互作用，以检查潜在的机制，改变或减缓异常核纤层蛋白A的表达和/或恢复正常的比例异常核纤层蛋白A。这些研究的最终目标是改善或对抗层粘连蛋白病和相关的衰老疾病，我们在这篇综述中讨论了目前的方法。
Scientific understanding of the genetic components of aging has increased in recent years, with several genes being identified as playing roles in the aging process and, potentially, longevity. In particular, genes encoding components of the nuclear lamina in eukaryotes have been increasingly well characterized, owing in part to their clinical significance in age-related diseases. This review focuses on one such gene, which encodes lamin A, a key component of the nuclear lamina. Genetic variation in this gene can give rise to lethal, early-onset diseases known as laminopathies. Here, we analyze the literature and conduct computational analyses of lamin A signaling and intracellular interactions in order to examine potential mechanisms for altering or slowing down aberrant Lamin A expression and/or for restoring the ratio of normal to aberrant lamin A. The ultimate goal of such studies is to ameliorate or combat laminopathies and related diseases of aging, and we provide a discussion of current approaches in this review.
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