Justin Parreno, Alyssa V. Cruz
ABSTRACT
Hutchinson-Gilford Progeria Syndrome (HGPS) is a condition characterized by signs of accelerated aging that present within the first year of life. Notable characteristics of children with HGPS include prominent superficial veins, failure to thrive, alopecia, as well as various skeletal and cardiovascular pathologies normally associated with advanced age. The discovery of the lamin A (C to T) gene mutation at position 1824 of the coding sequence has ushered in a greater understanding on the essential role of lamin A protein processing. In normal cells, processing prelamin A to mature lamin A is complete following the cleavage of end terminal amino acids. In HGPS, gene mutation results in the deletion of a Zmpste24/FACE1 splice site in prelamin A, preventing end terminal cleavage. Thus, prelamin A remains anchored due to C-terminal farnesylation. Lamin A eventually accumulates within the inner nuclear membrane of cells, resulting in disease pathology. The generation of experimental mouse models to understand the role of lamin A in normal, and HGPS cells have fostered the development of prospective HGPS treatments. Clinical trials investigating farnesyltransferase inhibitors (FTIs), statins, and bisphosphonates as HGPS treatments are currently underway. HGPS and the relationship to lamin A has also shed light on normal aging as accumulation of prelamin A has been revealed in aged (non-HGPS derived) cells.
KEYWORDS: progeria; lamin A; laminopathy; farnesylation; aging
Full text (PDF, 2.54MB)
Parreno J, Cruz AV. Accelerated Aging in Patients with Hutchinson-Gilford Progeria Syndrome: Clinical Signs, Molecular Causes, Treatments, and Insights into the Aging Process. UBCMJ. 2011 3(1):8-12.