What question did this study set out to answer?

To determine whether blocking prelamin A farnesylation with a farnesyltransferase inhibitor rescues nuclear shape abnormalities across human and mouse cellular models of progeroid syndromes.

August 29, 2005Proceedings of the National Academy of SciencesOpen Access

Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes

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To determine whether blocking prelamin A farnesylation with a farnesyltransferase inhibitor rescues nuclear shape abnormalities across human and mouse cellular models of progeroid syndromes.
Treated restrictive dermopathy (RD) human fibroblasts, Zmpste24-deficient mouse embryonic fibroblasts, and Hutchinson-Gilford progeria syndrome (HGPS) human fibroblasts with a farnesyltransferase inhibitor (FTI).
Tested FTI efficacy on two human fibroblast cell lines from atypical progeria patients harboring lamin A missense mutations without prelamin A accumulation.
Assessed prelamin A subcellular distribution at the nuclear envelope and quantified changes in the proportion of misshapen nuclei.
FTI treatment partially mislocalized prelamin A away from the nuclear envelope and significantly lowered nuclear shape abnormalities in RD fibroblasts (P < 0.0001) and Zmpste24-deficient mouse embryonic fibroblasts (P < 0.0001).
FTI exposure significantly reduced the frequency of nuclear shape defects in human HGPS fibroblasts (P < 0.0001).
FTI administration significantly improved nuclear morphology in two atypical progeria cell lines carrying lamin A missense mutations lacking prelamin A accumulation (P = 0.0003 and P < 0.0001).

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Implication

Experimental study demonstrates that farnesyltransferase inhibition restores normal nuclear shape in progeroid fibroblasts, suggesting a viable therapeutic strategy for lamin-linked progeria.

Cite This Study

Toth et al. (2005) studied this question.

synapsesocial.com/papers/6a97de0cd08ffd74dfc63327 https://doi.org/10.1073/pnas.0505767102

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Implication

Experimental study demonstrates that farnesyltransferase inhibition restores normal nuclear shape in progeroid fibroblasts, suggesting a viable therapeutic strategy for lamin-linked progeria.

Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes

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Discussion

Implication

Cite This Study

Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes

Key Points

Discussion

Implication

Cite This Study

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