The Accumulation of Progerin Underlies the Loss of Aortic Smooth Muscle Cells in Hutchinson-Gilford Progeria Syndrome.

ABSTRACT: Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disorder characterized by multiple aging-like phenotypes, including disease in large arteries. HGPS is caused by an internally truncated prelamin A (progerin) that cannot undergo the ZMPSTE24-mediated processing step that converts farnesyl-prelamin A to mature lamin A; consequently, progerin retains a carboxyl-terminal farnesyl lipid anchor. In cultured cells, progerin and full-length farnesyl-prelamin A (produced in Zmpste24 ^-/- cells) form an abnormal nuclear lamin meshwork accompanied by nuclear membrane ruptures and cell death; however, these proteins differ in their capacity to cause arterial disease. In a mouse model of HGPS (Lmna ^G609G), progerin causes loss of aortic smooth muscle cells (

SUBMITTER: Kim PH 

PROVIDER: S-EPMC11565845 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature