Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases

Alex Zhavoronkov, Zeljka McBride, Kieran J. Guinan, Maria Litovchenko, Alexey Moskalev

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

Scientific understanding of the genetic components of aging has increased in recent years, with several genes being identified as playing roles in the aging process and, potentially, longevity. In particular, genes encoding components of the nuclear lamina in eukaryotes have been increasingly well characterized, owing in part to their clinical significance in age-related diseases. This review focuses on one such gene, which encodes lamin A, a key component of the nuclear lamina. Genetic variation in this gene can give rise to lethal, early-onset diseases known as laminopathies. Here, we analyze the literature and conduct computational analyses of lamin A signaling and intracellular interactions in order to examine potential mechanisms for altering or slowing down aberrant Lamin A expression and/or for restoring the ratio of normal to aberrant lamin A. The ultimate goal of such studies is to ameliorate or combat laminopathies and related diseases of aging, and we provide a discussion of current approaches in this review.

Original languageEnglish (US)
Pages (from-to)1361-1389
Number of pages29
JournalJournal of Molecular Medicine
Volume90
Issue number12
DOIs
StatePublished - Dec 1 2012

Keywords

  • Age-related diseases
  • Aging
  • Lamin A
  • Laminopathies
  • Progeria

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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