Department of Biochemistry, Henry Wellcome Building, University of Leicester, Leicester LE1 9HN, UK.
Biochem Soc Trans. 2010 Feb;38(Pt 1):281-6. doi: 10.1042/BST0380281.
HGPS (Hutchinson-Gilford progeria syndrome) is a severe childhood disorder that appears to mimic an accelerated aging process. The disease is most commonly caused by gene mutations that disrupt the normal post-translational processing of lamin A, a structural component of the nuclear envelope. Impaired processing results in aberrant retention of a farnesyl group at the C-terminus of lamin A, leading to altered membrane dynamics. It has been widely proposed that persistence of the farnesyl moiety is the major factor responsible for the disease, prompting clinical trials of farnesyltransferase inhibitors to prevent lamin A farnesylation in children afflicted with HGPS. Although there is evidence implicating farnesylation in causing some of the cellular defects of HGPS, results of several recent studies suggest that aberrant lamin A farnesylation is not the only determinant of the disease. These findings have important implications for the design of treatments for this devastating disease.
HGPS（亨廷顿氏舞蹈症-吉福德早衰症）是一种严重的儿童疾病，其表现似乎类似于加速衰老过程。该疾病最常见的病因是基因突变，这些基因突变会破坏核膜结构成分 lamin A 的正常翻译后加工。异常的加工会导致 lamin A 的 C 末端发生异常的香叶基化基团保留，从而导致膜动力学改变。广泛认为，香叶基部分的持续存在是导致该疾病的主要因素，这促使人们进行法呢基转移酶抑制剂的临床试验，以防止患有 HGPS 的儿童的 lamin A 法尼基化。尽管有证据表明法尼基化会导致 HGPS 的一些细胞缺陷，但最近的几项研究结果表明，异常的 lamin A 法尼基化并非该疾病的唯一决定因素。这些发现对设计这种毁灭性疾病的治疗方法具有重要意义。
