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Aesthetic Plastic Surgery Jun 2022
Topics: Humans; Progeria; Rhinoplasty
PubMed: 34608515
DOI: 10.1007/s00266-021-02616-6 -
Nihon Ronen Igakkai Zasshi. Japanese... 2021
Topics: Humans; Progeria
PubMed: 34483167
DOI: 10.3143/geriatrics.58.409 -
Biochemical Society Transactions Dec 2017Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million... (Review)
Review
Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by a point mutation in exon 11 of the gene (c.1824C>T, p.G608G), resulting in the increased usage of a cryptic splice site and production of a truncated unprocessed lamin A protein named progerin. Since the genetic cause for HGPS was published in 2003, numerous potential treatment options have rapidly emerged. Strategies to interfere with the post-translational processing of lamin A, to enhance progerin clearance, or directly target the HGPS mutation to reduce the progerin-producing alternative splicing of the gene have been developed. Here, we give an up-to-date resume of the contributions made by our and other research groups to the growing list of different candidate treatment strategies that have been tested, both , in mouse models for HGPS and in clinical trials in HGPS patients.
Topics: Alternative Splicing; Animals; Cell Nucleus; Clinical Trials as Topic; Cytoplasm; Humans; Lamin Type A; Mice; Point Mutation; Progeria
PubMed: 29127216
DOI: 10.1042/BST20170141 -
Aging Cell Jul 2020Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular... (Review)
Review
Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. Till now clinical management of HGPS has largely relied on the treatment of manifestations and on the prevention of secondary complications, cure for the disease has not yet been established. Addressing this need cannot only benefit progeria patients but may also provide insights into intervention design for combating physiological aging. By using the systematic review approach, this article revisits the overall progress in the development of strategies for HGPS treatment over the last ten years, from 2010 to 2019. In total, 1,906 articles have been retrieved, of which 56 studies have been included for further analysis. Based on the articles analyzed, the trends in the use of different HGPS models, along with the prevalence, efficiency, and limitations of different reported treatment strategies, have been examined. Emerging strategies for preclinical studies, and possible targets for intervention development, have also been presented as avenues for future research.
Topics: Disease Progression; Humans; Progeria; Syndrome
PubMed: 32596971
DOI: 10.1111/acel.13175 -
Nucleus (Austin, Tex.) Jan 2018Hutchinson-Gilford progeria syndrome (HGPS) is a sporadic, autosomal dominant disorder characterized by premature and accelerated aging symptoms leading to death at the... (Review)
Review
Hutchinson-Gilford progeria syndrome (HGPS) is a sporadic, autosomal dominant disorder characterized by premature and accelerated aging symptoms leading to death at the mean age of 14.6 years usually due to cardiovascular complications. HGPS is caused by a de novo point mutation in the LMNA gene encoding the intermediate filament proteins lamins A and C which are structural components of the nuclear lamina. This mutation leads to the production of a truncated toxic form of lamin A, issued from aberrant splicing and called progerin. Progerin accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. HGPS cells and animal preclinical models have provided insights into the molecular and cellular pathways that underlie the disease and have also highlighted possible mechanisms involved in normal aging. This review reports recent medical advances and treatment approaches for patients affected with HGPS.
Topics: Animals; Cell Nucleus; Humans; Mutation; Progeria
PubMed: 29619863
DOI: 10.1080/19491034.2018.1460045 -
Giornale Italiano Di Dermatologia E... Jun 2015
Topics: Exons; Failure to Thrive; Heterozygote; Humans; Infant; Lamin Type A; Male; Mutation, Missense; Phenotype; Point Mutation; Progeria; Skin
PubMed: 25946677
DOI: No ID Found -
Trends in Molecular Medicine Oct 2006Genetic mutations that lead to an accumulation of farnesyl-prelamin A cause progeroid syndromes, including Hutchinson-Gilford progeria syndrome. It seemed possible that... (Review)
Review
Genetic mutations that lead to an accumulation of farnesyl-prelamin A cause progeroid syndromes, including Hutchinson-Gilford progeria syndrome. It seemed possible that the farnesylated form of prelamin A might be toxic to mammalian cells, accounting for all the disease phenotypes that are characteristic of progeria. This concept led to the hypothesis that protein farnesyltransferase inhibitors (FTIs) might ameliorate the disease phenotypes of progeria in mouse models. Thus far, two different mouse models of progeria have been examined. In both models, FTIs improved progeria-like disease phenotypes. Here, prelamin A post-translational processing is discussed and several mutations underlying human progeroid syndromes are described. In addition, recent data showing that FTIs ameliorate disease phenotypes in a pair of mouse models of progeria are discussed.
Topics: Alkyl and Aryl Transferases; Animals; Disease Models, Animal; Enzyme Inhibitors; Humans; Lamin Type A; Membrane Proteins; Metalloendopeptidases; Mice; Progeria; Protein Processing, Post-Translational
PubMed: 16942914
DOI: 10.1016/j.molmed.2006.08.006 -
Pediatrics Oct 2007Progeria (Hutchinson-Gilford progeria syndrome) is a rare genetic disorder that offers considerable insight into the biology of premature aging. This review summarizes... (Review)
Review
Progeria (Hutchinson-Gilford progeria syndrome) is a rare genetic disorder that offers considerable insight into the biology of premature aging. This review summarizes the clinical characteristics of this disease and the underlying mutation in the lamin A (LMNA) gene that results in this phenotype. Modifications in the processing of prelamin A through alterations in farnesylation are detailed, because this pathway offers a possible drug target. Finally, discussion of an ongoing clinical trial for these children, including possible parameters for evaluation, are discussed. In the span of less than a decade, this disease has progressed from an interesting phenotype to one in which the gene defect has been identified, animal models have been created and tested with drugs that target the primary disease pathway, and significant clinical baseline data for the support of a clinical trial have been obtained.
Topics: Alkyl and Aryl Transferases; Clinical Trials as Topic; Enzyme Inhibitors; Humans; Lamin Type A; Mutation; Progeria; Sequence Analysis, DNA
PubMed: 17908771
DOI: 10.1542/peds.2007-1356 -
The British Journal of Radiology Mar 1966
Topics: Child, Preschool; Humans; Male; Progeria; Radiography
PubMed: 5930811
DOI: 10.1259/0007-1285-39-459-224 -
Current Biology : CB Aug 2006The relationship between progerias--diseases that resemble premature aging--and the normal aging process has been a source of debate in the aging research community. A... (Review)
Review
The relationship between progerias--diseases that resemble premature aging--and the normal aging process has been a source of debate in the aging research community. A recent study finds that LMNA, a gene targeted for mutation in Hutchinson Gilford Progeria Syndrome, may control the onset of aging-associated decline in normal fibroblasts.
Topics: Age Factors; Aging; Cellular Senescence; Fibroblasts; Humans; Lamin Type A; Models, Biological; Progeria
PubMed: 16920618
DOI: 10.1016/j.cub.2006.07.029