ArticleProceedings of the National Academy of Sciences of the United States of America2005
Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers.
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Who cites it
215 citing papers in PubMed, 382 citations in OpenAlex.
- Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.Circulation · 2016Trial
- Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment.Neurology · 2013Trial
- Mutation-agnostic base editing of the progerin farnesylation site rescues Hutchinson-Gilford progeria syndrome phenotypes in neuromuscular organoids.Nature communications · 2026Article
- Progerin cross-linking stiffens the nucleus and impairs mechanosensation in Hutchinson-Gilford progeria syndrome.Journal of cell science · 2026Article
- Getting nuclear size just right - emerging mechanisms regulating nuclear scaling and morphology.Journal of cell science · 2026Review
- Farnesylated prelamin A induces fibroblast polarity defects in premature aging disorders by inhibiting nesprin-2-SUN2 LINC complex function.Journal of cell science · 2026Article
- Increased Telomere Mobility in Progeria is Restored by Isoprenylcysteine Carboxyl Methyltransferase Inhibition.bioRxiv : the preprint server for biology · 2026Article
- Tau oligomerization induces nuclear lamina invagination and chromatin remodeling in Alzheimer's disease.Acta neuropathologica · 2026Article
- Prelamin A accumulation overlaps increased vascular calcification in peripheral artery disease and regulates vascular smooth muscle cells mineralization in diabetes mellitus.Atherosclerosis plus · 2026Article
- Telomere shortening in laminopathic dilated cardiomyopathy.NPJ Regenerative medicine · 2026Article
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Baricitinib Augments Lonafarnib Therapy to Preserve Colonic Homeostasis and Microbial Balance in a Mouse Model of Progeria.Aging cell · 2025Article
- Counteracting lysosome defects alleviates the cellular senescence of Hutchinson-Gilford progeria syndrome.Science China. Life sciences · 2025Article
- Deregulated miR-145 and miR-27b in Hutchinson-Gilford progeria syndrome: implications for adipogenesis.Aging · 2025Article
- Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson-Gilford Progeria Syndrome.Diseases (Basel, Switzerland) · 2025Article
- Attenuated Nuclear Tension Regulates Progerin-Induced Mechanosensitive Nuclear Wrinkling and Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The accumulation of progerin underlies the loss of aortic smooth muscle cells in Hutchinson-Gilford progeria syndrome.Cell death & disease · 2025Article
- Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.Aging cell · 2025Article
- Baricitinib and Lonafarnib Synergistically Target Progerin and Inflammation, Improving Lifespan and Health in Progeria Mice.International journal of molecular sciences · 2025Article
- Adenine base editing rescues pathogenic phenotypes in tissue engineered vascular model of Hutchinson-Gilford progeria syndrome.APL bioengineering · 2025Article
155 more citing papers are in PubMed but not listed here.
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10 authors at 1 institution in 1 country.
Funding
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is characterized by dramatic premature aging and accelerated cardiovascular disease. HGPS is almost always caused by a de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, producing a truncated mutant protein termed "progerin." WT prelamin A is anchored to the nuclear envelope by a farnesyl isoprenoid lipid. Cleavage of the terminal 15 aa and the farnesyl group releases mature lamin A from this tether. In contrast, this cleavage site is deleted in progerin. We hypothesized that retention of the farnesyl group causes progerin to become permanently anchored in the nuclear membrane, disrupting proper nuclear scaffolding and causing the characteristic nuclear blebbing seen in HGPS cells. Also, we hypothesized that blocking farnesylation would decrease progerin toxicity. To test this hypothesis, the terminal CSIM sequence in progerin was mutated to SSIM, a sequence that cannot be farnesylated. SSIM progerin relocalized from the nuclear periphery into nucleoplasmic aggregates and produced no nuclear blebbing. Also, blocking farnesylation of authentic progerin in transiently transfected HeLa, HEK 293, and NIH 3T3 cells with farnesyltransferase inhibitors (FTIs) restored normal nuclear architecture. Last, treatment of both early- and late-passage human HGPS fibroblasts with FTIs resulted in significant reductions in nuclear blebbing. Our results suggest that treatment with FTIs represents a potential therapy for patients with HGPS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.