Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery

Alessandra Lo Cicero; Xavier Nissan

doi:10.1016/j.arr.2015.10.002

Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery

Ageing Res Rev. 2015 Nov;24(Pt B):343-8. doi: 10.1016/j.arr.2015.10.002. Epub 2015 Oct 22.

Authors

Alessandra Lo Cicero¹, Xavier Nissan²

Affiliations

¹ INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France; UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France; CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France.
² INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France; UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France; CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 5 rue Henri Desbruères, 91030 Evry Cedex, France. Electronic address: xnissan@istem.fr.

PMID: 26474742
DOI: 10.1016/j.arr.2015.10.002

Abstract

Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (p.G608G) of the LMNA, leading to the production of a mutated form of lamin A precursor called progerin. In HGPS, progerin accumulates in cells causing progressive molecular defects, including nuclear shape abnormalities, chromatin disorganization, damage to DNA and delays in cell proliferation. Here we report how, over the past five years, pluripotent stem cells have provided new insights into the study of HGPS and opened new original therapeutic perspectives to treat the disease.

Keywords: Ageing; Pluripotent stem cells; Progeria.

Publication types

Review

MeSH terms

Aging / physiology*
Drug Discovery
Humans
Lamin Type A / genetics*
Models, Biological
Mutation
Pluripotent Stem Cells / physiology*
Progeria / genetics
Progeria / metabolism

Substances

Lamin Type A
prelamin A