Síndrome de Progeria de Hutchinson-Gilford. Causas, investigación y tratamientos farmacológicos

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) also known as childhood progeria is a rare genetic disease characterized by accelerated aging beginning in early childhood. The phenotypic features of this syndrome are caused by alterations in the lamin A protein, fibrillar component of the nuclear lamina which maintain the structure of the nuclear envelope and participates in organization chromatin. Children with progeria have a point mutation in the LMNA gene which leads to the production of a permanently farnesylated mutant lamin A called progerin, that contribute to premature aging. In normal protein, this farnesyl group is removed, but this step does not take place in progeria and the progerin remain attached to the inner nuclear membrane, causing alterations in nuclear morphology. The use of several drugs that inhibit the farnesylation of progerin has been proposed as a promising therapeutic approach to reverse the adverse effects of progerin synthesis. Some studies have determined that progerin is also produced in normal individuals and increase with age, suggesting that these studies of progeria can shed light on the normal process of aging. In this paper the main aspects of HGPS such signs and symptoms, genetic basis, and how it has driven the discovery of strategies for treating the disease will be discussed.