Laboratory of Nuclear and Genomic Health, Centre for Cell and Chromosome Biology, Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge UB8 3PH, UK.
Biochem Soc Trans. 2010 Feb;38(Pt 1):287-91. doi: 10.1042/BST0380287.
HGPS (Hutchinson-Gilford progeria syndrome) is a rare genetic disease affecting children causing them to age and die prematurely. The disease is typically due to a point mutation in the coding sequence for the nuclear intermediate-type filament protein lamin A and gives rise to a dominant-negative splice variant named progerin. Accumulation of progerin within nuclei causes disruption to nuclear structure, causes and premature replicative senescence and increases apoptosis. Now it appears that accumulation of progerin may have more widespread effects than previously thought since the demonstration that the presence and distribution of some nucleolar proteins are also adversely affected in progeria cells. One of the major breakthroughs both in the lamin field and for this syndrome is that many of the cellular defects observed in HGPS patient cells and model systems can be restored after treatment with a class of compounds known as FTIs (farnesyltransferase inhibitors). Indeed, it is demonstrated that FTI-277 is able to completely restore nucleolar antigen localization in treated progeria cells. This is encouraging news for the HGPS patients who are currently undergoing clinical trials with FTI treatment.
HGPS（亨廷顿氏舞蹈症-进行性肌阵挛性癫痫）是一种罕见的遗传疾病，影响儿童，导致他们过早衰老和死亡。这种疾病通常是由于核中间丝蛋白 lamin A 的编码序列中的点突变引起的，并产生一种名为 progerin 的显性负剪接变异体。progerin 在核内的积累会破坏核结构，导致过早的复制性衰老和增加细胞凋亡。现在看来，progerin 的积累可能比以前认为的更广泛，因为已经证明核仁蛋白的存在和分布在早衰细胞中也受到不利影响。lamin 领域和这个综合征的一个主要突破是，在 HGPS 患者细胞和模型系统中观察到的许多细胞缺陷在经过一类称为 FTIs（法尼基转移酶抑制剂）的化合物处理后可以得到恢复。事实上，已经证明 FTI-277 能够完全恢复治疗性早衰细胞中的核仁抗原定位。对于目前正在接受 FTI 治疗临床试验的 HGPS 患者来说，这是一个令人鼓舞的消息。
