Brayson Daniel, Shanahan Catherine M
a King's College London, The James Black Centre , London , United Kingdom.
Nucleus. 2017 Jan 2;8(1):17-33. doi: 10.1080/19491034.2016.1260798.
The nuclear lamina is a critical structural domain for the maintenance of genomic stability and whole-cell mechanics. Mutations in the LMNA gene, which encodes nuclear A-type lamins lead to the disruption of these key cellular functions, resulting in a number of devastating diseases known as laminopathies. Cardiomyopathy is a common laminopathy and is highly penetrant with poor prognosis. To date, cell mechanical instability and dysregulation of gene expression have been proposed as the main mechanisms driving cardiac dysfunction, and indeed discoveries in these areas have provided some promising leads in terms of therapeutics. However, important questions remain unanswered regarding the role of lamin A dysfunction in the heart, including a potential role for the toxicity of lamin A precursors in LMNA cardiomyopathy, which has yet to be rigorously investigated.
核纤层是维持基因组稳定性和全细胞力学的关键结构域。编码核A型核纤层蛋白的LMNA基因突变会导致这些关键细胞功能的破坏，从而引发一系列被称为核纤层蛋白病的严重疾病。心肌病是一种常见的核纤层蛋白病，具有高度的外显率且预后不良。迄今为止，细胞机械不稳定性和基因表达失调被认为是导致心脏功能障碍的主要机制，并且这些领域的发现确实在治疗方面提供了一些有前景的线索。然而，关于核纤层蛋白A功能障碍在心脏中的作用，仍有一些重要问题未得到解答，包括核纤层蛋白A前体的毒性在LMNA心肌病中的潜在作用，这一点尚未得到严格研究。
