A5049324631- Nuclear Structure and Function
- RNA Research and Splicing
- Skin and Cellular Biology Research
- Ubiquitin and proteasome pathways
- Hair Growth and Disorders
- Retinoids in leukemia and cellular processes
- DNA Repair Mechanisms
- RNA regulation and disease
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Microtubule and mitosis dynamics
- Mesenchymal stem cell research
- Heat shock proteins research
- Cellular Mechanics and Interactions
- Vitamin C and Antioxidants Research
- Neurogenesis and neuroplasticity mechanisms
- Signaling Pathways in Disease
- Cellular transport and secretion
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Connexins and lens biology
- melanin and skin pigmentation
Technical University of Munich
2014-2025
Columbia University
2001-2010
Brigham and Women's Hospital
2010
National Institutes of Health
2010
National Heart Lung and Blood Institute
2010
Benaroya Research Institute
2010
Institut thématique Génétique, génomique et bioinformatique
2003
Centre National de la Recherche Scientifique
1997-1999
Sorbonne Université
1997-1999
Collège de France
1989-1996
Children with Hutchinson-Gilford progeria syndrome (HGPS) exhibit dramatically accelerated cardiovascular disease (CVD), causing death from myocardial infarction or stroke between the ages of 7 and 20 years. We undertook first histological comparative evaluation genetically confirmed HGPS CVD aging.
Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT) mutation within exon 11 LMNA, activating splice donor site that results in production dominant negative form lamin A protein, denoted progerin. Screening 150 skin biopsies unaffected individuals (newborn to 97 years) showed similar splicing event occurs vivo at low...
The expression of peripherin, an intermediate filament protein, had been shown by biochemical methods to be localized in the neurons PNS. Using immunohistochemical methods, we analyzed this more extensively during development rat and compared it with that low-molecular-mass neurofilament protein (NF-L), which is expressed every neuron CNS immunoreactivity NF-L first apparent at 25-somite stage (about 11 d) ventral horn spinal medulla posterior part rhombencephalon. peripherin appears...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by dramatic premature aging. Classic HGPS caused de novo point mutation in exon 11 (residue 1824, C --> T) of the LMNA gene, activating cryptic splice donor and resulting mutant lamin A (LA) protein termed "progerin/LADelta50" that lacks normal cleavage site to remove C-terminal farnesyl group. During interphase, irreversibly farnesylated progerin/LADelta50 anchors nuclear membrane causes characteristic...
Hutchinson–Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man accession no. 176670 ) is a rare disorder that characterized by segmental premature aging and death between 7 20 years of age from severe atherosclerosis. Mutations the LMNA gene are responsible for this syndrome. Approximately 80% HGPS cases caused G608 (GGC→GGT) mutation within exon 11 , which elicits deletion 50 aa near C terminus prelamin A. In article, we present evidence mutant lamin A (progerin)...
Summary Hutchinson–Gilford progeria syndrome ( HGPS , OMIM 176670) is a rare multisystem childhood premature aging disorder linked to mutations in the LMNA gene. The most common mutation found at position G608G within exon 11 of This results deletion 50 amino acids carboxyl‐terminal tail prelamin A, and truncated protein called progerin . Progerin only undergoes subset normal post‐translational modifications remains permanently farnesylated. Several attempts rescue cellular phenotype with...
ABSTRACT The small heat shock protein αβ-crystallin interacts with intermediate filament proteins. Using a co-sedimentation assay, we showed that in vitro binding of to peripherin and vimentin was temperature-dependent. Specifically, synthetic peptide representing the first ten residues involved this interaction. When cells were submitted different stress conditions such as serum starvation, hypertonic stress, or shock, observed dynamic reorganisation network, concomitant recruitment...
We have previously shown that glial cell line-derived neurotrophic factor (GDNF), in addition to promoting the survival of dopaminergic neurons cultures from embryonic rat ventral mesencephalon, also increases activity choline acetyltransferase (ChAT) cranial motoneurons present these (Zurn et al.: Neuroreport 6:113–118, 1994). By using intermediate filament protein peripherin as a motoneuron marker, we report here GDNF number well length their neurites. Brain-derived (BDNF) and ciliary...
Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disorder that leads to death at an average age of 14.7 years due myocardial infarction or stroke, is caused by mutations in the LMNA gene. Nearly 90% HGPS cases carry G608G mutation within exon 11 generates truncated prelamin A protein “progerin”. Progerin accumulates cells and induces senescence cellular organismal levels. Children suffering from develop numerous clinical features overlap with normal aging, including...
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This elicits an internal deletion 50 amino acids in the carboxyl-terminus prelamin A. The truncated protein, progerin, retains farnesylated cysteine at its carboxyl terminus, modification involved HGPS pathogenesis. Inhibition protein farnesylation has been shown to improve abnormal morphology...
Abstract Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with preclinically documented impact on those mechanisms. However, extensive functional effects remain essentially unexplored. We have undertaken systematic comparative study three main treatments currently administered or proposed...
Abstract Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS caused by mutations in LMNA , the gene that encodes nuclear lamins A C. most common mutation subjects de novo single-base pair...
Hutchinson–Gilford progeria syndrome (HGPS) is an accelerated aging disorder caused by point mutation in LMNA encoding A-type nuclear lamins. The mutations activate a cryptic splice donor site, resulting expression of truncated, prenylated prelamin A called progerin. Expression progerin leads to alterations morphology, which may underlie pathology HGPS. We generated transgenic mice expressing epidermis under control keratin 14 promoter. had severe abnormalities morphology skin keratinocyte...
Summary Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by segmental accelerated aging and early death from coronary artery disease or stroke. Nearly 90% of HGPS sufferers carry G608G mutation within exon 11 LMNA, producing truncated form prelamin A, referred to as “progerin”. Here, we report the isolation naïve multipotent skin-derived precursor (SKP) cells dermal fibroblast cultures donors. These spheres express neural crest marker, nestin, in...
// Diana Gabriel 1 , Dinah Dorith Shafry Leslie B. Gordon 2,3 and Karima Djabali Department of Dermatology, Epigenetics Aging, TUM School Medicine, Technische Universität München, Garching-Munich, Germany 2 Pediatrics, Alpert Medical Brown University Hasbro Children’s Hospital, Providence, RI, USA 3 Boston Hospital Harvard School, Boston, MA, Correspondence to: Djabali, email: Keywords : progerin, lamin, Ionafarnib, sulforaphane, autophagy, Gerotarget Received February 25,...
Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder that causes accelerated aging, due to a pathogenic variant in the LMNA gene. This results production of progerin, defective protein disrupts nuclear lamina's structure. In our study, we conducted histopathological analysis various organs LmnaG609G/G609G mouse model, which commonly used study HGPS. The objective this was show progerin accumulation drives systemic but organ-specific tissue damage and aging...
Hutchinson–Gilford progeria syndrome (HGPS) is a rare, fatal, and premature aging disorder caused by progerin, truncated form of lamin A that disrupts nuclear architecture, induces systemic inflammation, accelerates senescence. While the farnesyltransferase inhibitor lonafarnib extends lifespan limiting progerin farnesylation, it does not address chronic inflammation or senescence-associated secretory phenotype (SASP), which worsens disease progression. In this study, we investigated...
Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain shape and stability nuclear envelope addition regulating DNA replication, transcription, proliferation differentiation. The mutation results deletion 50 amino acids from carboxy-terminal region prelamin A, producing truncated, farnesylated protein progerin....
Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare premature aging disorder that leads to death at an average age of 14.7 years due myocardial infarction or stroke. The most common mutation in HGPS position G608G (GGC>GGT) within exon 11 the LMNA gene. This results deletion 50 amino acids carboxyl-terminal tail prelamin A, producing truncated farnesylated protein called progerin. Lamins play important roles organization and structure nucleus. nuclear build-up progerin causes...
Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease that causes premature aging symptoms, such as vascular diseases, lipodystrophy, loss of bone mineral density, and alopecia. HGPS mostly linked to heterozygous de novo mutation in the LMNA gene (c.1824 C > T; p.G608G), resulting production truncated prelamin A protein called “progerin”. Progerin accumulation nuclear dysfunction, senescence, apoptosis. Here, we examined effects baricitinib (Bar), an FDA-approved JAK/STAT...
ABSTRACT Hair follicle cycling is an exquisitely regulated and dynamic process consisting of phases growth, regression quiescence. The transitions between the are governed by a growing number regulatory proteins, including transcription factors. hairless (hr) gene encodes putative factor that highly expressed in skin, where it appears to be essential regulator during catagen hair follicle. In mice, as well humans with congenital atrichia, absence hr function initiates premature abnormal due...