Liu Baohua, Zhou Zhongjun
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
Histol Histopathol. 2008 Jun;23(6):747-63. doi: 10.14670/HH-23.747.
Lamin A/C belongs to type V intermediate filaments and constitutes the nuclear lamina and nuclear matrix, where a variety of nuclear activities occur. Lamin A/C protein is firstly synthesized as a precursor and is further proteolytically processed by the zinc metallo-proteinase Ste24 (Zmpste24). Lamin A/C mutations cause a series of human diseases, collectively called laminopathies, the most severe of which is Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arises due to an unsuccessful maturation of prelamin A. Although the exact underlying molecular mechanisms are still poorly understood, genomic instability, defective nuclear mechanics and mechanotransduction, have been hypothesized to be responsible for laminopathy-based premature ageing. Removal of unprocessed prelamin A (progerin) or rescue of defective DNA repair could be potential therapeutic strategies for the treatment of HGPS in future.
核纤层蛋白A/C属于V型中间丝，构成核纤层和核基质，多种核活动在此发生。核纤层蛋白A/C最初以前体形式合成，随后由锌金属蛋白酶Ste24（Zmpste24）进行蛋白水解加工。核纤层蛋白A/C突变会导致一系列人类疾病，统称为核纤层蛋白病，其中最严重的是哈钦森-吉尔福德早衰综合征（HGPS）和由于前体核纤层蛋白A成熟失败而引发的限制性皮肤病（RD）。尽管确切的潜在分子机制仍知之甚少，但基因组不稳定、有缺陷的核力学和机械转导被认为是导致基于核纤层蛋白病的早衰的原因。去除未加工的前体核纤层蛋白A（早老素）或挽救有缺陷的DNA修复可能是未来治疗HGPS的潜在治疗策略。
