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Title
Molecular insights into the premature aging disease progeria
AuthorFoisner, Roland ; Vidak, Sandra
Published in
Histochemistry and Cell Biology, New York, 2016, Vol. 145, Issue 4, page 401-417
PublishedNew York : Springer, 2016
LanguageEnglish
Document typeJournal Article
Keywords (EN)lamins / premature aging / progeria / nucleoplasmic lamins / chromatin / signaling / adult stem cells / senescence / hutchinson-gilford-progeria / a-type lamins / nf-kappa-b / atypical werners-syndrome / intermediate-filament proteins / polypeptide 2-alpha lap2-alpha / extracellular-matrix proteins / cell-cycle progression / lmna gene mutation / adult stem-cells
Project-/ReportnumberP 26492-B20
ISSN0948-6143
URNurn:nbn:at:at-ubmuw:3-1708 Persistent Identifier (URN)
DOI10.1007/s00418-016-1411-1 
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 The work is publicly available
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Abstract (English)

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests.

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CC-BY-License (4.0)Creative Commons Attribution 4.0 International License