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.
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Conference Article| January 19 2010
Lamin A-linked progerias: is farnesylation the be all and end all?
Dawn T. Smallwood;
Publisher: Portland Press Ltd
Received: July 02 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
Dawn T. Smallwood, Sue Shackleton; Lamin A-linked progerias: is farnesylation the be all and end all?. Biochem Soc Trans 1 February 2010; 38 (1): 281–286. doi: https://doi.org/10.1042/BST0380281
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