Lamin A-linked progerias: is farnesylation the be all and end all?

Date

2010-01-19

Advisors

Journal Title

Journal ISSN

ISSN

1470-8752

Volume Title

Publisher

Portland Press

Type

Article

Peer reviewed

Yes

Abstract

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.

Description

The Publisher's final version can be found by following the DOI link.

Keywords

Progeria, Prenylation, Farnesyltranstransferase, Nuclear Envelope, Lamin Type A, Human

Citation

Smallwood, D.T., Shackleton, S. (2010) Lamin A-linked progerias: is farnesylation the be all and end all? Biochemical Society Transactions, 38(1), pp. 281–286.

Rights

Research Institute

Institute for Allied Health Sciences Research