Nuclear damages and oxidative stress: new perspectives for laminopathies

  • G. Lattanzi
  • S. Marmiroli
  • A. Facchini
  • N.M. Maraldi | nadirmario.maraldi@unibo.it Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy, Italy.

Abstract

Mutations in genes encoding nuclear envelope proteins, particularly LMNA encoding the A-type lamins, cause a broad range of diverse diseases, referred to as laminopathies. The astonishing variety of diseased phenotypes suggests that different mechanisms could be involved in the pathogenesis of laminopathies. In this review we will focus mainly on two of these pathogenic mechanisms: the nuclear damages affecting the chromatin organization, and the oxidative stress causing un-repairable DNA damages. Alteration in the nuclear profile and in chromatin organization, which are particularly impressive in systemic laminopathies whose cells undergo premature senescence, are mainly due to accumulation of unprocessed prelamin A. The toxic effect of these molecular species, which interfere with chromatin-associated proteins, transcription factors, and signaling pathways, could be reduced by drugs which reduce their farnesylation and/or stability. In particular, inhibitors of farnesyl transferase (FTIs), have been proved to be active in rescuing the altered cellular phenotype, and statins, also in association with other drugs, have been included into pilot clinical trials. The identification of a mechanism that accounts for accumulation of un-repairable DNA damage due to reactive oxygen species (ROS) generation in laminopathic cells, similar to that found in other muscular dystrophies (MDs) caused by altered expression of extracellular matrix (ECM) components, suggests that anti-oxidant therapeutic strategies might prove beneficial to laminopathic patients.

Downloads

Download data is not yet available.
Published
2012-10-18
Section
Reviews
Supporting Agencies
this work was supported by grants from the A.I.Pro.Sa.B., Italy, the Italian MIUR PRIN 2008 to G.L. and FIRB to N.M.Maraldi, and by “5 per mille” 2010, I.O.R., Bologna
Keywords:
laminopathies, nuclear envelope, chromatin, muscular dystrophies, progeria, oxidative stress, DNA damage
Statistics
Abstract views: 704

PDF: 236
HTML: 191
Share it

PlumX Metrics

PlumX Metrics provide insights into the ways people interact with individual pieces of research output (articles, conference proceedings, book chapters, and many more) in the online environment. Examples include, when research is mentioned in the news or is tweeted about. Collectively known as PlumX Metrics, these metrics are divided into five categories to help make sense of the huge amounts of data involved and to enable analysis by comparing like with like.

How to Cite
Lattanzi, G., Marmiroli, S., Facchini, A., & Maraldi, N. (2012). Nuclear damages and oxidative stress: new perspectives for laminopathies. European Journal of Histochemistry, 56(4), e45. https://doi.org/10.4081/ejh.2012.e45

Most read articles by the same author(s)