Review
Biochemistry & Molecular Biology
Jon Macicior, Beatriz Marcos-Ramiro, Silvia Ortega-Gutierrez
Summary: Progeria is a rare genetic disorder caused by a point mutation in the lamin A gene, resulting in abnormal accumulation of progerin. Patients typically die prematurely at the average age of 14.5 due to significant alterations in the cardiovascular system, bones, skin, and overall growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Noelle J. Batista, Sanket G. Desai, Alexis M. Perez, Alexa Finkelstein, Rachel Radigan, Manrose Singh, Aaron Landman, Brian Drittel, Daniella Abramov, Mina Ahsan, Samantha Cornwell, Dong Zhang
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome caused by a point mutation in the LMNA gene. The resulting mutant protein, progerin, behaves in a dominant-negative fashion, leading to cellular and molecular changes similar to normal aging cells. However, HGPS manifests in an accelerated manner and primarily affects connective tissues. Epigenetic changes in HGPS have been studied and may play a crucial role in the disease's pathogenesis. Recent treatments for HGPS have shown important effects at a cellular level, improving symptoms and increasing lifespan.
Review
Medicine, Research & Experimental
Bulmaro Cisneros, Ian Garcia-Aguirre, Marlon De Ita, Isabel Arrieta-Cruz, Haydee Rosas-Vargas
Summary: Aging is the gradual decline of physical and psychological functions in humans, accompanied by the onset of chronic-degenerative diseases. The study of Hutchinson-Gilford progeria syndrome (HGPS) has provided insights into understanding the aging process. HGPS is caused by a genetic mutation that leads to the synthesis of progerin, a mutant version of lamin A. However, the mechanisms by which progerin induces detrimental alterations at the cellular and systemic levels are not fully understood.
ARCHIVES OF MEDICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xiaojing Mao, Zheng-Mei Xiong, Huijing Xue, Markus A. Brown, Yantenew G. Gete, Reynold Yu, Linlin Sun, Kan Cao
Summary: This study investigated the molecular mechanisms and potential therapeutic applications for the skin abnormalities in Hutchinson-Gilford progeria syndrome (HGPS) by studying early skin development using patient-derived induced pluripotent stem cells (iPSCs). The findings showed that HGPS iPSCs displayed accelerated commitment to the keratinocyte lineage and decreased expression of the WNT transcription factor LEF1 during iPSCs-keratinocytes differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Neil Daily, Julian Elson, Tetsuro Wakatsuki
Summary: Researchers used aging-in-a-dish models, specifically cardiomyocytes derived from induced pluripotent stem cells of progeria syndrome patients, to evaluate the effects of proarrhythmia drugs and found that the progeria cells were more sensitive, showing a higher risk of arrhythmia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Wayne A. Cabral, Chris Stephan, Masahiko Terajima, Abhirami A. Thaivalappil, Owen Blanchard, Urraca L. Tavarez, Narisu Narisu, Tingfen Yan, Stephen M. Wincovitch, Yuki Taga, Mitsuo Yamauchi, Kenneth M. Kozloff, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation in the LMNA gene, resulting in the production of the toxic progerin protein. This study used a mouse model of HGPS to investigate the mechanisms of bone loss associated with the disease. The findings revealed abnormal bone formation, reduced bone mass, and increased fragility in the HGPS mice. The study also identified abnormal differentiation of osteoblasts and upregulation of adipogenic genes as contributing factors to the bone abnormalities in HGPS.
Article
Cell Biology
Cristina Capanni, Elisa Schena, Maria Letizia Di Giampietro, Alessandra Montecucco, Elisabetta Mattioli, Giovanna Lattanzi
Summary: This study reveals the crucial role of prelamin A in the recruitment of 53BP1 and DNA damage repair during stress response. It modulates the structure and affinity of Lamin A/C complexes, affecting subsequent DNA repair processes and contributing to cellular defense response.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Pratik Talukder, Arunima Saha, Sohini Roy, Gargi Ghosh, Debshikha Dutta Roy, Snejuti Barua
Summary: Hutchinson-Gilford progeria syndrome is a rare genetic disease characterized by accelerated aging and reduced life span. Research is being conducted to understand the causes of this disease and develop treatment options, but the success rate is low.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2023)
Review
Genetics & Heredity
Md Mominur Rahman, Kazi Sayma Ferdous, Muniruddin Ahmed, Mohammad Touhidul Islam, Md Robin Khan, Asma Perveen, Ghulam Md Ashraf, Md Sahab Uddin
Summary: Lamin A/C encoded by the LMNA gene is crucial for nuclear structure maintenance, with mutations leading to laminopathies such as Hutchinson-Gilford progeria syndrome (HGPS). HGPS, caused by abnormal splicing of the LMNA gene and progerin protein production, results in premature aging and is an area of emerging research for developing effective treatments.
CURRENT GENE THERAPY
(2021)
Article
Cell Biology
Junyeop Kim, Yerim Hwang, Sumin Kim, Yujung Chang, Yunkyung Kim, Youngeun Kwon, Jongpil Kim
Summary: Partial cellular reprogramming using Oct4, Sox2, Klf4, and c-Myc can rejuvenate cells and reduce aged-cell phenotypes. In this study, we demonstrated that activating the endogenous Oct4 gene through CRISPR/dCas9 system can ameliorate aging in a mouse model of Hutchinson-Gilford progeria syndrome. The activated Oct4 expression not only induced epigenetic remodeling and suppressed progerin accumulation, but also rescued vascular pathological features and lifespan shortening. These findings suggest that CRISPR/dCas9-mediated Oct4 activation could be a promising strategy for treating geriatric diseases.
Article
Cell Biology
Haihuan Lin, Juliane Mensch, Maria Haschke, Kathrin Jager, Brigitte Kottgen, Jens Dernedde, Evelyn Orso, Michael Walter
Summary: Establishing five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT demonstrated enhanced proliferative lifespan and reduced senescence signs, with growth increase and phenotype improvement independent of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for phenotype improvement, suggesting implications for therapeutic strategies in HGP and other premature aging syndromes.
Article
Cardiac & Cardiovascular Systems
Anahita Mojiri, Brandon K. Walther, Chongming Jiang, Gianfranco Matrone, Rhonda Holgate, Qiu Xu, Elisa Morales, Guangyu Wang, Jianhua Gu, Rongfu Wang, John P. Cooke
Summary: The study on a unique HGPS cell model demonstrated the impact of telomere repair on vascular cell aging, suggesting telomerase mRNA as a potential effective therapeutic approach for HGPS. Research on endothelial cells differentiated from patients with HGPS showed that hTERT treatment improved cellular function, restored endothelial function, and reduced the release of inflammatory markers.
EUROPEAN HEART JOURNAL
(2021)
Article
Cardiac & Cardiovascular Systems
Alvaro Macias, J. Jaime Diaz-Larrosa, Yaazan Blanco, Victor Fanjul, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria Jesus Andres-Manzano, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Andrew Allan, David Filgueiras-Rama, Jose Jalife, Vicente Andres
Summary: This study found that heart tissue from Hutchinson-Gilford progeria syndrome (HGPS) patients has structural and electrophysiological defects, including disruption of the t-tubular system, shortened sarcomeres, bradycardia, and atrio-ventricular conduction abnormalities. Chronic treatment with low-dose paclitaxel partially corrected these abnormalities.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cell Biology
So-mi Kang, Seungwoon Seo, Eun Ju Song, Okhee Kweon, Ah-hyeon Jo, Soyoung Park, Tae-Gyun Woo, Bae-Hoon Kim, Goo Taeg Oh, Bum-Joon Park
Summary: This study found that aberrant splicing of the LMNA gene in HGPS patients leads to the production of a mutant protein called Progerin, and Progerinin can reduce its expression and improve aging phenotypes. Through experiments on HGPS model mice, it was observed that Progerinin can restore cardiac function and correct arterial abnormalities, providing encouraging evidence for the efficacy of Progerinin in treating cardiac dysfunction in HGPS.
Article
Cell Biology
Yosra Bejaoui, Aleem Razzaq, Noha A. Yousri, Junko Oshima, Andre Megarbane, Abeer Qannan, Ramya Pottabatula, Tanvir Alam, George M. Martin, Henning F. Horn, Thomas Haaf, Steve Horvath, Nady El Hajj
Summary: In this study, the researchers conducted a genome-wide methylation analysis on blood DNA samples from patients with progeroid laminopathies. They found DNA methylation alterations at specific CpG sites and regions, and identified possible pathways/mechanisms involved in the accelerated aging process of progeroid laminopathies. They also observed significant differences in methylation patterns between different subtypes of progeroid laminopathies.
Article
Multidisciplinary Sciences
Alessandra Lo Cicero, Manoubia Saidani, Jennifer Allouche, Anne Laure Egesipe, Lucile Hoch, Celine Bruge, Sabine Sigaudy, Annachiara De Sandre-Giovannoli, Nicolas Levy, Christine Baldeschi, Xavier Nissan
SCIENTIFIC REPORTS
(2018)
Article
Materials Science, Biomaterials
Patricia R. Pitrez, Luis Estronca, Helena Vazao, Anne-Laure Egesipe, Amelie Le Corf, Claire Navarro, Nicolas Levy, Annachiara De Sandre-Giovannoli, Xavier Nissan, Lino Ferreira
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2018)
Article
Materials Science, Biomaterials
Patricia R. Pitrez, Luis Estronca, Helena Vazao, Anne-Laure Egesipe, Amelie Le Corf, Claire Navarro, Nicolas Levy, Annachiara De Sandre-Giovannoli, Xavier Nissan, Lino Ferreira
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2018)
Article
Multidisciplinary Sciences
Lucile Hoch, Sara F. Henriques, Celine Bruge, Justine Marsolier, Manon Benabides, Nathalie Bourg, Johana Tournois, Gurvan Mahe, Lise Morizur, Margot Jarrige, Anne Bigot, Isabelle Richard, Xavier Nissan
SCIENTIFIC REPORTS
(2019)
Article
Food Science & Technology
Sylvie Morel, Nathalie Saint, Manon Vitou, Alessandra Lo Cicero, Xavier Nissan, Barbara Vernus, Beatrice Chabi, Anne Bonnieu, Gerald Hugon, Francoise Fons, Guillaume Bouguet, Sylvie Rapior, Gilles Carnac
JOURNAL OF FUNCTIONAL FOODS
(2019)
Article
Biochemical Research Methods
Solenn M. Guilbert, Deborah Cardoso, Nicolas Levy, Antoine Muchir, Xavier Nissan
Summary: Drug repurposing is an efficient and low-cost strategy, which has made significant progress in treating rare diseases in recent years.
Article
Multidisciplinary Sciences
Patricia R. Pitrez, Luis Estronca, Luis Miguel Monteiro, Guillem Colell, Helena Vazao, Deolinda Santinha, Karim Harhouri, Daniel Thornton, Claire Navarro, Anne-Laure Egesipe, Tania Carvalho, Rodrigo L. Dos Santos, Nicolas Levy, James C. Smith, Joao Pedro de Magalhaes, Alessandro Ori, Andreia Bernardo, Annachiara De Sandre-Giovannoli, Xavier Nissan, Anna Rosell, Lino Ferreira
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Adrien Moreau, Jean-Baptiste Reisqs, Helene Delanoe-Ayari, Marion Pierre, Alexandre Janin, Antoine Deliniere, Francis Bessiere, Albano C. Meli, Azzouz Charrabi, Estele Lafont, Camille Valla, Delphine Bauer, Elodie Morel, Vincent Gache, Gilles Millat, Xavier Nissan, Adele Faucherre, Chris Jopling, Sylvain Richard, Alexandre Mejat, Philippe Chevalier
Summary: This study investigated the early electrical myogenic signature of arrhythmogenic cardiomyopathy (ACM) in a patient with a DSC2 gene mutation. Results showed abnormal repolarization dynamics in ACM patients and a short QT interval. The study confirmed a myogenic origin of ACM electrical instability and suggested the use of class 1 and 3 antiarrhythmic drugs in ACM patients with increased ventricular repolarization reserve.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Celine Bruge, Marine Geoffroy, Manon Benabides, Emilie Pellier, Evelyne Gicquel, Jamila Dhiab, Lucile Hoch, Isabelle Richard, Xavier Nissan
Summary: This study introduces a platform for modeling LGMD using hiPSC, providing a renewable and alternative source of skMC for studying LGMD.
Meeting Abstract
Cell & Tissue Engineering
Patricia Pitrez, Luis Estronca, Luis Monteiro, Deolinda Santinha, Karim Harhouri, Claire Navarro, Anne-Laure Egesipe, Tania Cavalho, Joao-Pedro Magalhaes, Alessandro Ori, Andreia Bernardo, Annachiara De Sandre-Giovannoli, Xavier Nissan, Anna Rosell, Lino Ferreira
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Cell & Tissue Engineering
Deolinda Santinha, Andreia Vilaca, Annachiara De Sandre-Giovannoli, Xavier Nissan, Alessandro Ori, Lino Ferreira
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Cell & Tissue Engineering
Luis Estronca, Vitor Franciso, Patricia Pitrez, Ines Honorio, Lara Carvalho, Helena Vazao, Josephine Blersh, Akhilesh Rai, Xavier Nissan, Ulrich Simon, Mario Graos, Leonor Saude, Lino Ferreira
TISSUE ENGINEERING PART A
(2022)
Article
Pharmacology & Pharmacy
Lucile Hoch, Nathalie Bourg, Fanny Degrugillier, Celine Bruge, Manon Benabides, Emilie Pellier, Johana Tournois, Gurvan Mahe, Nicolas Maignan, Jack Dawe, Maxime Georges, David Papazian, Nik Subramanian, Stephanie Simon, Pascale Fanen, Cedric Delevoye, Isabelle Richard, Xavier Nissan
Summary: This study investigates the protein degradation defect in LGMD R3 and identifies the HDAC inhibitor givinostat as a potential therapeutic option. The findings provide new treatment strategies for LGMD R3 patients and offer insights for the treatment of other genetic diseases with similar protein degradation defects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Luis Estronca, Vitor Francisco, Patricia Pitrez, Ines Honorio, Lara Carvalho, Helena Vazao, Josephine Blersch, Akhilesh Rai, Xavier Nissan, Ulrich Simon, Mario Graos, Leonor Saude, Lino Ferreira
Summary: The study evaluated the vascular bioactivity and safety of 30 different nanoparticle formulations using a zebrafish model and personal humanized models. The results showed that the toxicity profile of the nanoparticles was influenced by the age of endothelial cells and vascular network format, with endothelial cells cultured in flow conditions showing less susceptibility to cytotoxicity effects. The study highlights the importance of in vitro hiPSC-derived vascular systems in screening interactions with vascular nanomaterials.
NANOSCALE HORIZONS
(2021)
Article
Multidisciplinary Sciences
Alessandra Lo Cicero, Manoubia Saidani, Jennifer Allouche, Anne Laure Egesipe, Lucile Hoch, Celine Bruge, Sabine Sigaudy, Annachiara De Sandre-Giovannoli, Nicolas Levy, Christine Baldeschi, Xavier Nissan
SCIENTIFIC REPORTS
(2018)
