Prelamin A Farnesylation and Progeroid Syndromes*

@article{Young2006PrelaminAF,
  title={Prelamin A Farnesylation and Progeroid Syndromes*},
  author={Stephen G. Young and Margarita D. Meta and Shao H. Yang and Loren G. Fong},
  journal={Journal of Biological Chemistry},
  year={2006},
  volume={281},
  pages={39741 - 39745}
}
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant prelamin A that is farnesylated but cannot be further processed to mature lamin A. A more severe progeroid disorder, restrictive dermopathy (RD), is caused by the loss of the prelamin A-processing enzyme, ZMPSTE24. The absence of ZMPSTE24 prevents the endoproteolytic processing of farnesyl-prelamin A to mature lamin A and leads to the accumulation of farnesyl-prelamin A. In both HGPS… 

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The clinical characteristics of this disease, the underlying mutation in the lamin A (LMNA) gene that results in this phenotype and the recent advances in treatment strategies are summarized.
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Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice
TLDR
These novel mice provide a robust model to study the effects of farnesylated prelamin A during physiological aging andcultured embryonic fibroblasts from LmnaL648R/l648R mice have aberrant nuclear morphology that is reversible by treatment with a protein farnesytransferase inhibitor.
Epithelial stem cells In Hutchinson-Gilford progeria syndrome
TLDR
Novel findings are offered about the intricate molecular disease mechanisms underlying HGPS and RD, which include increased inflammation, prolonged expression of the lamin B receptor gene, and arrested skin development.
Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes
TLDR
Two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA are presented, and farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients.
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