Raška Ivan
Charles University in Prague, First Faculty of Medicine, Institute of Cellular Biology and Pathology, and Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Department of Cell Biology, Albertov 4, 128 01, Prague, Czech Republic.
Interdiscip Toxicol. 2010 Sep;3(3):89-93. doi: 10.2478/v10102-010-0018-y.
Ranged among laminopathies, Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned.
作为核纤层蛋白病的一种，哈钦森-吉尔福德早衰综合征是一种涉及早衰的综合征，通常导致在10至14岁之间死亡，主要原因是心肌梗死或中风。在本次讲座中，我将概述分子细胞生物学研究的重要性，这些研究导致了对这种罕见综合征背后基本机制的发现。在大多数情况下，其遗传基础是核纤层蛋白A基因第1824位核苷酸的突变。在这个位置，胞嘧啶被胸腺嘧啶取代，从而在核纤层蛋白A的前体mRNA内产生一个隐蔽的剪接位点。这导致产生异常的核纤层蛋白A，即早老素，它在细胞中的存在具有有害的显性效应。根据细胞类型和组织的不同，早老素会诱发不同组织中各不相同的多种缺陷。还将提及目前应对这种可怕疾病的努力。
