Dorado Beatriz, Andrés Vicente
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), CIBER de Enfermedades Cardiovasculares, Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), CIBER de Enfermedades Cardiovasculares, Madrid, Spain.
Curr Opin Cell Biol. 2017 Jun;46:17-25. doi: 10.1016/j.ceb.2016.12.005. Epub 2017 Jan 10.
Lamin A is a nuclear intermediate filament protein with important structural and regulatory roles in most differentiated mammalian cells. Excessive accumulation of its precursor prelamin A or the mutant form called 'progerin' causes premature aging syndromes. Progeroid 'laminopathies' are characterized by severe cardiovascular problems (cardiac electrical defects, vascular calcification and stiffening, atherosclerosis, myocardial infarction, and stroke) and premature death. Here, we review studies in cell and mouse models and patients that are unraveling how abnormal prelamin A and progerin accumulation accelerates cardiovascular disease and aging. This knowledge is essential for developing effective therapies to treat progeria and may help identify new mechanisms underlying normal aging.
核纤层蛋白A是一种核中间丝蛋白，在大多数分化的哺乳动物细胞中具有重要的结构和调节作用。其前体前核纤层蛋白A或称为“早老素”的突变形式的过度积累会导致早衰综合征。类早衰“核纤层蛋白病”的特征是严重的心血管问题（心脏电缺陷、血管钙化和硬化、动脉粥样硬化、心肌梗死和中风）以及过早死亡。在这里，我们综述了细胞和小鼠模型以及患者的研究，这些研究正在揭示异常的前核纤层蛋白A和早老素积累如何加速心血管疾病和衰老。这些知识对于开发治疗早衰的有效疗法至关重要，并且可能有助于确定正常衰老的新机制。
