Contents

06 February 2013
Vol 5, Issue 171

About The Cover

Cover image expansion

ONLINE COVER Lamentable Lamin. When fully functional, nuclear lamins form a filament meshwork—the nuclear lamina (white)—along the inside of the nuclear membrane (purple; shown with a nuclear pore). The nuclear lamina constitutes a scaffold that interacts with chromatin [a protein (red)–DNA (blue) complex] and influences nuclear functions such as transcriptional regulation. In patients with Hutchinson-Gilford progeria syndrome (HGPS), a genetic premature aging disease, improper processing of lamin creates an aberrant farnesylated version that gives rise to misshapen nuclei and HGPS’s characteristic pathophysiology. A recently completed high-profile clinical trial tested the therapeutic effects of a protein farnesyltransferase inhibitor (lonafarnib) in HGPS patients. In this week’s Perspective, Young et al. discuss the rationale for inhibiting farnesyltransferase, the limitations of this therapeutic approach, and potential new strategies for treating HGPS. [CREDIT: C. BICKEL/SCIENCE TRANSLATIONAL MEDICINE]