886 results match your criteria Hutchinson-Gilford Progeria


Transient expression of an adenine base editor corrects the Hutchinson-Gilford progeria syndrome mutation and improves the skin phenotype in mice.

Nat Commun 2022 Jun 2;13(1):3068. Epub 2022 Jun 2.

Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature ageing disorder caused by a point mutation in the LMNA gene (LMNA c.1824 C > T), resulting in the production of a detrimental protein called progerin. Adenine base editors recently emerged with a promising potential for HGPS gene therapy. Read More

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Impaired LEF1 Activation Accelerates iPSC-Derived Keratinocytes Differentiation in Hutchinson-Gilford Progeria Syndrome.

Int J Mol Sci 2022 May 14;23(10). Epub 2022 May 14.

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20817, USA.

Hutchinson-Gilford progeria syndrome (HGPS) is a detrimental premature aging disease caused by a point mutation in the human gene. This mutation results in the abnormal accumulation of a truncated pre-lamin A protein called progerin. Among the drastically accelerated signs of aging in HGPS patients, severe skin phenotypes such as alopecia and sclerotic skins always develop with the disease progression. Read More

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Hutchinson-Gilford Progeria paves the way for novel targeted anti-aging therapies.

Med (N Y) 2021 04 9;2(4):353-354. Epub 2021 Apr 9.

Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore, Singapore; Singapore Institute of Clinical Sciences, A∗STAR, Singapore, 117609, Singapore.

Hutchinson-Gilford Progeria is an accelerated aging syndrome caused by permanently farnesylated mutant lamin A, termed progerin. Recently, the FDA approved Lonafarnib, a farnesyltransferase inhibitor, to treat progeria, while Koblan and colleagues used novel gene editing methods to target the root cause of this disease by correcting the LMNA mutation. Read More

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Progeria: a perspective on potential drug targets and treatment strategies.

Expert Opin Ther Targets 2022 May 19;26(5):393-399. Epub 2022 May 19.

New Mechanisms of Atherosclerosis Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

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Genetic basis of cardiovascular aging is at the core of human longevity.

Authors:
Ali J Marian

J Cardiovasc Aging 2022 14;2(2). Epub 2022 Apr 14.

Center for Cardiovascular Genetics, Institute of Molecular Medicine and Department of Medicine, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA.

Aging is an archetypical complex process influenced by genetic and environmental factors. Genetic variants impart a gradient of effect sizes, albeit the effect sizes seem to be skewed toward those with small effect sizes. On one end of the spectrum are the rare monogenic premature aging syndromes, such as Hutchinson Gilford Progeria Syndrome, whereby single nucleotide changes lead to rapidly progressive premature aging. Read More

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Progeria-a Rare Genetic Condition with Accelerated Ageing Process.

Appl Biochem Biotechnol 2022 Apr 21. Epub 2022 Apr 21.

Department of Biotechnology, University of Engineering and Management, University Area, Plot, Street Number 03, Action Area III, B/5, Newtown, Kolkata, West Bengal, 700156, India.

Progeria is a rare genetic disease which is characterised by accelerated ageing and reduced life span. There are differing types of progeria, but the classic type is Hutchinson-Gilford progeria syndrome (HGPS). Within a year of birth, people suffering from it start showing several features such as very low weight, scleroderma, osteoporosis and loss of hair. Read More

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Monitoring of Chromatin Organization at the Nuclear Pore Complex, Inner Nuclear Membrane, and Nuclear Interior in Live Cells by Fluorescence Ratiometric Imaging of Chromatin (FRIC).

Methods Mol Biol 2022 ;2502:151-160

Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.

The image analysis tool FRIC (Fluorescence Ratiometric Imaging of Chromatin) quantitatively monitors dynamic spatiotemporal distribution of euchromatin and total chromatin in live cells. A vector (pTandemH) assures stoichiometrically constant expression of the histone variants Histone 3.3 and Histone 2B, fused to EGFP and mCherry, respectively. Read More

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[Progerin and Its Role in Accelerated and Natural Aging].

Authors:
M I Mosevitsky

Mol Biol (Mosk) 2022 Mar-Apr;56(2):181-205

Konstantinov St. Petersburg Nuclear Physics Institute, Kurchatov Research Center, Gatchina, 188300 Russia.

Well-known theories of aging suggest that a certain metabolic defect negatively affects vital activity of the cell, be it oxidative stress, the accumulation of lesions in DNA, the exhaustion of telomeres, or distorted epigenetic processes. The theory of aging considered in the review postulates that an accumulation of progerin on the inner side of the nuclear envelope underlies the above defects. Progerin is a defective precursor of the lamin A nuclear matrix protein in which the C-terminal cysteine, which is removed normally, is retained and modified with a hydrophobic oligoisoprene chain. Read More

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Transcatheter aortic valve implantation in patients with age ≤70 years: experience from two leading structural heart disease centers.

Minerva Cardiol Angiol 2022 Mar 25. Epub 2022 Mar 25.

Department of Cardiac Surgery and Heart Transplantation, San Camillo Forlanini Hospital, Rome, Italy.

Background: Transcatheter aortic valve implantation (TAVI) is emerging a an appealing management strategy for patients with severe aortic stenosis at intermediate, high or exceedingly high risk, but its risk-benefit profile in younger patients is less certain. We aimed at exploring the outlook of patients aged 70 years or less and undergoing TAVI at 2 high-volume Italian institituions.

Methods: We retrospectively collected baseline, imaging, procedural and outcome features of patients with age ≤70 years in whom TAVI was attempted at participating centers between 2012 and 2021. Read More

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Cell immortalization facilitates prelamin A clearance by increasing both cell proliferation and autophagic flux.

Aging (Albany NY) 2022 03 8;14(5):2047-2061. Epub 2022 Mar 8.

Department of Biochemistry, Complutense University, Madrid, Spain.

Hutchinson-Gilford Progeria Syndrome is an ultrarare disease which is characterized by an accelerated senescence phenotype with deleterious consequences to people suffering this pathology. The production of an abnormal protein derived from lamin A, called progerin, presents a farnesylated domain, which is not eliminated by the causal mutation of the disease, and accumulates in the interior of the nucleus, provoking a disruption of nuclear membrane, chromatin organization and an altered gene expression. The mutation in these patients occurs in a single nucleotide change, which creates a de novo splicing site, producing a shorter version of the protein. Read More

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Rapid and robust derivation of mesenchymal stem cells from human pluripotent stem cells via temporal induction of neuralized ectoderm.

Cell Biosci 2022 Mar 15;12(1):31. Epub 2022 Mar 15.

School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Background: Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. Read More

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Carotid artery dissection in Hutchinson-Gilford Progeria: a case report.

BMC Pediatr 2022 03 14;22(1):135. Epub 2022 Mar 14.

Paediatrics Department, Complexo Hospitalario Universitario de Ferrol, Sergas, Spain.

Background: Strokes in the paediatric age group have their own epidemiology and aetiology and are frequently misdiagnosed. As in the adult population, they present some risk factors that must be identified. Cerebral arteriopathies as a cause of paediatric ischaemic stroke present a very diverse aetiology and morphology. Read More

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Splicing Variants, Protein-Protein Interactions, and Drug Targeting in Hutchinson-Gilford Progeria Syndrome and Small Cell Lung Cancer.

Genes (Basel) 2022 01 18;13(2). Epub 2022 Jan 18.

Rare Disease R&D Center, PRG S&T Co., Ltd., Busan 46241, Korea.

Alternative splicing (AS) is a biological operation that enables a messenger RNA to encode protein variants (isoforms) that give one gene several functions or properties. This process provides one of the major sources of use for understanding the proteomic diversity of multicellular organisms. In combination with post-translational modifications, it contributes to generating a variety of protein-protein interactions (PPIs) that are essential to cellular homeostasis or proteostasis. Read More

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January 2022

Lysophosphatidic Acid Receptor 3 Promotes Mitochondrial Homeostasis against Oxidative Stress: Potential Therapeutic Approaches for Hutchinson-Gilford Progeria Syndrome.

Antioxidants (Basel) 2022 Feb 10;11(2). Epub 2022 Feb 10.

Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.

Lysophosphatidic acid (LPA) is a growth factor-like lipid mediator that regulates various physiological functions via activation of multiple LPA G protein-coupled receptors. We previously reported that LPA suppresses oxidative stress in premature aging Hutchinson-Gilford progeria syndrome (HGPS) patient fibroblasts via its type 3 receptor (LPA). Mitochondria have been suggested to be the primary origin of oxidative stress via the overproduction of reactive oxygen species (ROS). Read More

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February 2022

MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients' Cells.

Cells 2022 02 10;11(4). Epub 2022 Feb 10.

Marseille Medical Genetics (MMG), INSERM U 1251, Aix Marseille Université, 13005 Marseille, France.

Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Read More

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February 2022

Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.

Proc Natl Acad Sci U S A 2022 03;119(9)

Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032;

Prelamin A is a farnesylated precursor of lamin A, a nuclear lamina protein. Accumulation of the farnesylated prelamin A variant progerin, with an internal deletion including its processing site, causes Hutchinson-Gilford progeria syndrome. Loss-of-function mutations in , which encodes the prelamin A processing enzyme, lead to accumulation of full-length farnesylated prelamin A and cause related progeroid disorders. Read More

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Nuclear lamins: Structure and function in mechanobiology.

APL Bioeng 2022 Mar 1;6(1):011503. Epub 2022 Feb 1.

Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

Nuclear lamins are type V intermediate filament proteins that polymerize into complex filamentous meshworks at the nuclear periphery and in less structured forms throughout the nucleoplasm. Lamins interact with a wide range of nuclear proteins and are involved in numerous nuclear and cellular functions. Within the nucleus, they play roles in chromatin organization and gene regulation, nuclear shape, size, and mechanics, and the organization and anchorage of nuclear pore complexes. Read More

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Vascular smooth muscle cell aging: Insights from Hutchinson-Gilford progeria syndrome.

Clin Investig Arterioscler 2022 Feb 3. Epub 2022 Feb 3.

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.

Vascular smooth muscle cells (VSMCs) constitute the principal cellular component of the medial layer of arteries and are responsible for vessel contraction and relaxation in response to blood flow. Alterations in VSMCs can hinder vascular system function, leading to vascular stiffness, calcification and atherosclerosis, which in turn may result in life-threatening complications. Pathological changes in VSMCs typically correlate with chronological age; however, there are certain conditions and diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), that can accelerate this process, resulting in premature vascular aging. Read More

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February 2022

miR-376a-3p and miR-376b-3p overexpression in Hutchinson-Gilford progeria fibroblasts inhibits cell proliferation and induces premature senescence.

iScience 2022 Feb 10;25(2):103757. Epub 2022 Jan 10.

Aix Marseille Univ, APHM, INSERM, MMG, Hôpital la Timone, Service de Biologie Cellulaire, 27 Bd Jean Moulin, Marseille, France.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder, in which an abnormal and toxic protein called progerin, accumulates in cell nuclei, leading to major cellular defects. Among them, chromatin remodeling drives gene expression changes, including miRNA dysregulation. In our study, we evaluated miRNA expression profiles in HGPS and control fibroblasts. Read More

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February 2022

Phasor map analysis to investigate Hutchinson-Gilford progeria cell under polarization-resolved optical scanning microscopy.

Sci Rep 2022 01 31;12(1):1679. Epub 2022 Jan 31.

Nanoscopy and [email protected], Italian Institute of Technology (IIT), Via Enrico Melen 83, 16152, Genova, Italy.

Polarized light scanning microscopy is a non-invasive and contrast-enhancing technique to investigate anisotropic specimens and chiral organizations. However, such arrangements suffer from insensitivity to confined blend of structures at sub-diffraction level. Here for the first time, we present that the pixel-by-pixel polarization modulation converted to an image phasor approach issues an insightful view of cells to distinguish anomalous subcellular organizations. Read More

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January 2022

DNA methylation signatures in Blood DNA of Hutchinson-Gilford Progeria syndrome.

Aging Cell 2022 02 19;21(2):e13555. Epub 2022 Jan 19.

College of Health and Life Sciences, Qatar Foundation, Hamad Bin Khalifa University, Doha, Qatar.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder caused by mutations in the LMNA gene and characterized by premature and accelerated aging beginning in childhood. In this study, we performed the first genome-wide methylation analysis on blood DNA of 15 patients with progeroid laminopathies using Infinium Methylation EPIC arrays including 8 patients with classical HGPS. We could observe DNA methylation alterations at 61 CpG sites as well as 32 significant regions following a 5 Kb tiling analysis. Read More

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February 2022

Novel Compound Heterozygous Variants in the Gene in a Russian Patient with Meier-Gorlin Syndrome.

Appl Clin Genet 2022 6;15:1-10. Epub 2022 Jan 6.

Molecular Genetics Laboratory № 3 The Shared Resource Centre "Genome", Federal State Budgetary Scientific Institution Research Centre for Medical Genetics named after Academician N.P. Bochkov, Moscow, Russian Federation.

Background: Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (, and ). Read More

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January 2022

Cardiovascular manifestations of Hutchinson-Gilford progeria syndrome.

Cardiol Young 2022 Jan 13:1-3. Epub 2022 Jan 13.

Department of Paediatric Cardiology, Referral Centre for Congenital Cardiac Defects, CHUC, Portugal, Coimbra, Portugal.

Cardiovascular complications are the most frequent cause of death in patients with the Hutchinson-Gilford progeria syndrome. However, due to its rarity, studying the course of cardiac abnormalities has been a challenge. The cardiovascular phenotype helps to provide greater insight into the natural history of these abnormalities. Read More

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January 2022

Endothelial and systemic upregulation of miR-34a-5p fine-tunes senescence in progeria.

Aging (Albany NY) 2022 01 12;14(1):195-224. Epub 2022 Jan 12.

Max Perutz Labs, Center for Medical Biochemistry, Medical University of Vienna, Vienna Biocenter Campus (VBC), Vienna A-1030, Austria.

Endothelial defects significantly contribute to cardiovascular pathology in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Using an endothelium-specific progeria mouse model, we identify a novel, endothelium-specific microRNA (miR) signature linked to the p53-senescence pathway and a senescence-associated secretory phenotype (SASP). Progerin-expressing endothelial cells exert profound cell-non-autonomous effects initiating senescence in non-endothelial cell populations and causing immune cell infiltrates around blood vessels. Read More

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January 2022

Progerin-expressing endothelial cells are unable to adapt to shear stress.

Biophys J 2022 02 6;121(4):620-628. Epub 2022 Jan 6.

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia. Electronic address:

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a single-point mutation in the lamin A gene, resulting in a truncated and farnesylated form of lamin A. This mutant lamin A protein, known as progerin, accumulates at the periphery of the nuclear lamina, resulting in both an abnormal nuclear morphology and nuclear stiffening. Patients with HGPS experience rapid onset of atherosclerosis, with death from heart attack or stroke as teenagers. Read More

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February 2022

Efficacy of Cord Blood Cell Therapy for Hutchinson-Gilford Progeria Syndrome-A Case Report.

Int J Mol Sci 2021 Nov 15;22(22). Epub 2021 Nov 15.

Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disorder characterized by short stature and atherosclerosis-induced death within teenage years. A 13-year-old male diagnosed with HGPS was administered three intravenous infusions of allogeneic cord blood (CB) cells from unrelated donors at four-month intervals to evaluate the safety and its therapeutic efficacy. Adverse events were monitored in addition to height, weight, laboratory blood tests, joint range of motion (ROM), and carotid Doppler. Read More

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November 2021

Cardiovascular Progerin Suppression and Lamin A Restoration Rescue Hutchinson-Gilford Progeria Syndrome.

Circulation 2021 11 25;144(22):1777-1794. Epub 2021 Oct 25.

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain (A.S.-L., C.G.-G., P.G., M.J.A.-M., V.F., M.R.H., A.M., L.d.C., E.C., J.V., B.D., V.A.).

Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease is provoked by progerin, a variant of lamin A expressed in most differentiated cells. Patients look healthy at birth, and symptoms typically emerge in the first or second year of life. Read More

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November 2021

Rhinoplasty on Hutchinson-Gilford Progeria Syndrome Patient.

Aesthetic Plast Surg 2021 Oct 4. Epub 2021 Oct 4.

Department of Plastic, Reconstructive and Aesthetic Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 200 - 00128, Rome, Italy.

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October 2021

Hutchinson-Gilford Progeria Syndrome (Hgps) and Application of Gene Therapy Based Crispr/Cas Technology as A Promising Innovative Treatment Approach.

Recent Pat Biotechnol 2021 ;15(4):266-285

Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Ponekkara P.O., Kochi, Kerala 682041, India.

Background: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria of childhood or progeria is a rare, rapid, autosomal dominant genetic disorder characterized by premature aging which occurs shortly after birth. HGPS occurs as a result of de novo point mutation in the gene recognized as LMNA gene that encodes two proteins, Lamin A protein and Lamin C protein which are the structural components of the nuclear envelope. Mutations in the gene trigger abnormal splicing and induce internal deletion of 50 amino acids leading to the development of a truncated form of Lamin A protein known as Progerin. Read More

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December 2021