ArticleThe Journal of clinical investigation2016
Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 100 citations in OpenAlex.
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Design, synthesis and evaluation of clickable photoaffinity probes for nuclear lamins.Bioorganic & medicinal chemistry letters · 2025Article
- Exploring senescence markers as potential drivers of osteoarthritis pain in aging adults.Experimental gerontology · 2025Review
- Counteracting lysosome defects alleviates the cellular senescence of Hutchinson-Gilford progeria syndrome.Science China. Life sciences · 2025Article
- Analysis of Beta-Dystroglycan in Different Cell Models of Senescence.International journal of molecular sciences · 2025Article
- Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson-Gilford Progeria Syndrome.Diseases (Basel, Switzerland) · 2025Article
- Targeting CRM1 for Progeria Syndrome Therapy.Aging cell · 2025Article
- Intermediate filaments and their associated molecules.Journal of biomedical research · 2025Article
- Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.Cell communication and signaling : CCS · 2024Review
- Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.npj aging · 2024Review
- Nuclear envelope budding inhibition slows down progerin-induced aging process.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Anticancer potential of decursin, decursinol angelate, and decursinol fromFood science & nutrition · 2024Review
- The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice.Aging cell · 2024Article
- Lamin A/C facilitates DNA damage response by modulating ATM signaling and homologous recombination pathways.Animal cells and systems · 2024Article
- Understanding cellular senescence: pathways involved, therapeutics and longevity aiding.Cell cycle (Georgetown, Tex.) · 2023Review
- Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS.Cells · 2023Review
- [Research advances in pharmacotherapy for rare diseases in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury.Neurobiology of disease · 2023Review
- Review
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Given this observation, we performed a random screening of a chemical library and identified 3 compounds (JH1, JH4, and JH13) that efficiently block progerin-lamin A/C binding. These 3 chemicals, particularly JH4, alleviated nuclear deformation and reversed senescence markers characteristic of HGPS cells, including growth arrest and senescence-associated β-gal (SA-β-gal) activity. We then used microarray-based analysis to demonstrate that JH4 is able to rescue defects of cell-cycle progression in both HGPS and aged cells. Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan. Together, these findings indicate that specific inhibitors with the ability to block pathological progerin-lamin A/C binding may represent a promising strategy for improving lifespan and health in both HGPS and normal aging.
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