Hutchinson-Gilford progeria syndrome (HGPS) is a rare humangenetic disease that leads to a severe premature ageingphenotype, caused by mutations in the LMNA gene. TheLMNA gene codes for lamin-A and lamin-C proteins, whichare structural components of the nuclear lamina. HGPS isusually caused by a de novo C1824T mutation that leads tothe accumulation of a dominant negative form of lamin-Acalled progerin. Progerin also accumulates physiologically innormal ageing cells as a rare splicing form of lamin-A transcripts.From this perspective, HGPS cells seem to be goodcandidates for the study of the physiological mechanisms ofageing. Progerin accumulation leads to faster cellular senescence,stem cell depletion and the progeroid phenotype. Tissuesof mesodermic origin are especially affected by HGPS.HGPS patients usually have a bad quality of life and, withcurrent treatments, their life expectancy does not exceedtheir second decade at best. Though progerin can be expressedin almost any tissue, when death occurs, it is usuallydue to cardiovascular complications. In HGPS, severe epigeneticalterations have been reported. Histone-covalentmodifications are radically different from control specimens,with the tendency to lose the bipartition into euchromatinand heterochromatin. This is reflected in an altered spatialcompartmentalization and conformation of chromatin withinthe nucleus. Moreover, it seems that microRNAs and microRNAbiosynthesis might play a role in HGPS. Exemplary inthis connection is the suggested protective effect of miR-9on the central nervous system of affected individuals. Thismini-review will report on the state of the art of HGPS epigenetics,and there will be a discussion of how epigeneticalterations in HGPS cells can alter the cellular metabolismand lead to the systemic syndrome.
|Numero di pagine||7|
|Stato di pubblicazione||Published - 2014|
All Science Journal Classification (ASJC) codes